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1.
Sci Adv ; 10(28): eadn3628, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38985879

RESUMEN

The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source of tumor-specific antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling and immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions and experimental validation experiments, we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs, including two peptides that can trigger an immune response in humanized mice. We identify a subset of 33 tumor-specific long noncoding RNAs expressing novel cancer antigens shared by more than 10% of the HCC samples analyzed, which, when combined, cover a large proportion of the patients. The results of the study open avenues for extending the range of anticancer vaccines.


Asunto(s)
Antígenos de Neoplasias , Carcinoma Hepatocelular , Neoplasias Hepáticas , Sistemas de Lectura Abierta , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Animales , Ratones , Estudios de Cohortes , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Micropéptidos
2.
FASEB J ; 38(13): e23772, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38963337

RESUMEN

Ovarian cancer is one of the most common gynecologic malignancies that has a poor prognosis. THUMPD3-AS1 is an oncogenic long noncoding RNA (lncRNA) in several cancers. Moreover, miR-320d is downregulated and inhibited proliferation in ovarian cancer cells, whereas ARF1 was upregulated and promoted the malignant progression in epithelial ovarian cancer. Nevertheless, the role of THUMPD3-AS1 in ovarian cancer and the underlying mechanism has yet to be elucidated. Human normal ovarian epithelial cells (IOSE80) and ovarian cancer cell lines (CAVO3, A2780, SKOV3, OVCAR3, and HEY) were adopted for in vitro experiments. The functional roles of THUMPD3-AS1 in cell viability and apoptosis were determined using CCK-8, flow cytometry, and TUNEL assays. Western blot was performed to assess the protein levels of ARF1, Bax, Bcl-2, and caspase 3, whereas RT-qPCR was applied to measure ARF1 mRNA, THUMPD3-AS1, and miR-320d levels. The targeting relationship between miR-320d and THUMPD3-AS1 or ARF1 was validated with dual luciferase assay. THUMPD3-AS1 and ARF1 were highly expressed in ovarian cancer cells, whereas miR-320d level was lowly expressed. THUMPD3-AS1 knockdown was able to repress cell viability and accelerate apoptosis of OVCAR3 and SKOV3 cells. Also, THUMPD3-AS1 acted as a sponge of miR-320d, preventing the degradation of ARF1. MiR-320d downregulation reversed the tumor suppressive function induced by THUMPD3-AS1 depletion. Additionally, miR-320d overexpression inhibited ovarian cancer cell viability and accelerated apoptosis, which was overturned by overexpression of ARF1. THUMPD3-AS1 inhibited ovarian cancer cell apoptosis by modulation of miR-320d/ARF1 axis. The discoveries might provide a prospective target for ovarian cancer treatment.


Asunto(s)
Factor 1 de Ribosilacion-ADP , Apoptosis , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias Ováricas , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Apoptosis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Factor 1 de Ribosilacion-ADP/metabolismo , Factor 1 de Ribosilacion-ADP/genética , Proliferación Celular
3.
Arq Bras Cardiol ; 121(6): e20230675, 2024.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-38958296

RESUMEN

BACKGROUND: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. OBJECTIVE: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. METHODS: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. RESULTS: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. CONCLUSION: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis.


FUNDAMENTO: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. OBJETIVO: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. MÉTODOS: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. RESULTADOS: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. CONCLUSÃO: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1.


Asunto(s)
Apoptosis , Doxorrubicina , MicroARNs , Miocitos Cardíacos , ARN Largo no Codificante , Humanos , Doxorrubicina/farmacología , ARN Largo no Codificante/genética , Apoptosis/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Antibióticos Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Reproducibilidad de los Resultados , Western Blotting , Citometría de Flujo , ARN Endógeno Competitivo
4.
Neoplasma ; 71(3): 219-230, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38958710

RESUMEN

Epidermal growth factor receptor (EGFR) gene exon 19 in-frame deletion (19del) and exon 21 L858R point mutation (21L858R mutation) are prevalent mutations in lung adenocarcinoma. Lung adenocarcinoma patients with 19del presented with a better prognosis than the 21L858R mutation under the same epidermal growth factor receptor tyrosine kinase inhibitor treatment. Our study aimed to uncover the expression of long non-coding RNA LOC105376794 between 19del and 21L858R mutation, and explore the mechanism that regulates cells' biological behavior and gefitinib sensitivity in lung adenocarcinoma cells with 19del. Transcriptome sequencing was conducted to identify differentially expressed lncRNAs between EGFR 19del and 21L858R mutation in serum through the DNBSEQ Platform. Protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway were conducted to analyze the relationship between lncRNAs and mRNAs through STRING and Dr. TOM. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of lncRNA LOC105376794 in serum and cells. Loss-of-function experiments were used to validate the biological function and gefitinib sensitivity of LOC105376794 in lung adenocarcinoma cells. Protein levels were detected by western blotting. Through transcriptome resequencing and RT-qPCR, we found the expression levels of LOC105376794 in serum were increased in the 19del group compared with the 21L858R mutation group. Inhibition of LOC105376794 promoted proliferation, migration and invasion, and reduced apoptosis of HCC827 and PC-9 cells. The low expression of LOC105376794 reduced gefitinib sensitivity in PC-9 cells. Mechanistically, we found that the knockdown of LOC105376794 suppressed activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway and facilitated the expression of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation. LOC105376794 altered cell biological behavior and gefitinib sensitivity of lung adenocarcinoma cells with 19del through the ATF4/CHOP signaling pathway and the expression of ERK phosphorylation. The results further illustrated the fact that lung adenocarcinoma patients with 19del presented with a more favorable clinical outcome and provided a theoretical basis for treatment strategy for lung adenocarcinoma patients with 19del.


Asunto(s)
Adenocarcinoma del Pulmón , Movimiento Celular , Resistencia a Antineoplásicos , Receptores ErbB , Gefitinib , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , Gefitinib/farmacología , ARN Largo no Codificante/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Fosforilación , Línea Celular Tumoral , Mutación , Proliferación Celular , Invasividad Neoplásica , Regulación Neoplásica de la Expresión Génica , Factor de Transcripción Activador 4
5.
Clin Exp Med ; 24(1): 146, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960924

RESUMEN

Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Ferroptosis/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología
6.
Medicine (Baltimore) ; 103(27): e38750, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968515

RESUMEN

BACKGROUND: Bladder cancer (BLCA) is a prevalent and aggressive cancer associated with high mortality and poor prognosis. Currently, studies on the role of disulfidptosis-related long non-coding RNAs (DRLs) in BLCA are limited. This study aims to construct a prognostic model based on DRLs to improve the accuracy of survival predictions for patients and identify novel targets for therapeutic intervention in BLCA management. METHODS: Transcriptomic and clinical datasets for patients with BLCA were obtained from The Cancer Genome Atlas. Using multivariate Cox regression and least absolute shrinkage and selection operator techniques, a risk prognostic signature defined by DRLs was developed. The model's accuracy and prognostic relevance were assessed through Kaplan-Meier survival plots, receiver operating characteristic curves, concordance index, and principal component analysis. Functional and pathway enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, were conducted to elucidate the underlying biological processes. Immune cell infiltration was quantified using the CIBERSORT algorithm. Differences and functions of immune cells in different risk groups were evaluated through single-sample Gene Set Enrichment Analysis. The Tumor Immune Dysfunction and Exclusion predictor and tumor mutational burden (TMB) assessments were utilized to gauge the likelihood of response to immunotherapy. Drug sensitivity predictions were made using the Genomics of Drug Sensitivity in Cancer database. RESULTS: A robust 8-DRL risk prognostic model, comprising LINC00513, SMARCA5-AS1, MIR4435-2HG, MIR4713HG, AL122035.1, AL359762.3, AC006160.1, and AL590428.1, was identified as an independent prognostic indicator. This model demonstrated strong predictive power for overall survival in patients with BLCA, revealing significant disparities between high- and low-risk groups regarding tumor microenvironment, immune infiltration, immune functions, TMB, Tumor Immune Dysfunction and Exclusion scores, and drug susceptibility. CONCLUSION: This study introduces an innovative prognostic signature of 8 DRLs, offering a valuable prognostic tool and potential therapeutic targets for bladder carcinoma. The findings have significant implications for TMB, the immune landscape, and patient responsiveness to immunotherapy and targeted treatments.


Asunto(s)
ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Humanos , ARN Largo no Codificante/genética , Pronóstico , Biomarcadores de Tumor/genética , Masculino , Estimación de Kaplan-Meier , Femenino , Transcriptoma , Curva ROC
7.
Clin Exp Med ; 24(1): 145, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960987

RESUMEN

Pyroptosis-related long-noncoding RNAs (PRlncRNAs) play an important role in cancer progression. However, their role in lung squamous cell carcinoma (LUSC) is unclear. A risk model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis based on RNA sequencing data from The Cancer Genome Atlas database. The LUSC cohort was divided into high- and low-risk groups based on the median risk score. For the prognostic value of the model, the Kaplan-Meier analysis, log-rank test, and Cox regression analysis were performed. A nomogram was constructed to predict the prognosis of patients, using a risk score and clinical parameters such as age, sex, clinical stage, and tumor node metastasis classification (TNM) stage. Afterwards, six common algorithms were employed to assess the invasion of immune cells. The Gene Set Enrichment Analysis (GSEA) was conducted to identify differences between patients at high and low risk. Furthermore, the pRRophetic package was employed to forecast the half-maximal inhibitory doses of prevalent chemotherapeutic drugs, while the tumor immune dysfunction and exclusion score was computed to anticipate the response to immunotherapy. The expression levels of the seven PRlncRNAs were examined in both LUSC and normal lung epithelial cell lines using RT-qPCR. Proliferation, migration, and invasion assays were also carried out to investigate the role of MIR193BHG in LUSC cells. Patients in the low-risk group showed prolonged survival in the total cohort or subgroup analysis. The Cox regression analysis showed that the risk model could act as an independent prognostic factor for patients with LUSC. The results of GSEA analysis revealed that the high-risk group showed enrichment of cytokine pathways, Janus tyrosine kinase/signal transducer and activator of the transcription signalling pathway, and Toll-like receptor pathway. Conversely, the low-risk group showed enrichment of several gene repair pathways. Furthermore, the risk score was positively correlated with immune cell infiltration. Moreover, patients in the high-risk category showed reduced responsiveness to conventional chemotherapeutic medications and immunotherapy. The majority of the long noncoding RNAs in the risk model were confirmed to be overexpressed in LUSC cell lines compared to normal lung epithelial cell lines by in vitro tests. Further studies have shown that downregulating the expression of MIR193BHG may inhibit the growth, movement, and infiltration capabilities of LUSC cells, whereas increasing the expression of MIR193BHG could enhance these malignant tendencies. This study found that PRlncRNAs were linked to the prognosis of LUSC patients. The risk model, evaluated across various clinical parameters and treatment modalities, shows potential as a future reference for clinical applications.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Piroptosis , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Masculino , Femenino , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Pronóstico , Piroptosis/genética , Inmunoterapia , Persona de Mediana Edad , Nomogramas , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Anciano , Línea Celular Tumoral
8.
Cell Biol Toxicol ; 40(1): 53, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970639

RESUMEN

Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.


Asunto(s)
Apoptosis , Retinopatía Diabética , ARN no Traducido , Transducción de Señal , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Retinopatía Diabética/terapia , Humanos , Apoptosis/genética , Transducción de Señal/genética , Animales , ARN no Traducido/genética , ARN no Traducido/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Retina/metabolismo , Retina/patología
9.
Cardiovasc Diabetol ; 23(1): 227, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951895

RESUMEN

In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM.


Asunto(s)
Cardiomiopatías Diabéticas , ARN Circular , ARN Largo no Codificante , Humanos , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/metabolismo , Animales , ARN Circular/genética , ARN Circular/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Regulación de la Expresión Génica , ARN no Traducido/genética , ARN no Traducido/metabolismo , Transducción de Señal , Miocardio/patología , Miocardio/metabolismo
10.
PeerJ ; 12: e17661, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978758

RESUMEN

Leaf mustard (Brassica juncea L. Czern & Coss), an important vegetable crop, experiences pronounced adversity due to seasonal drought stress, particularly at the seed germination stage. Although there is partial comprehension of drought-responsive genes, the role of long non-coding RNAs (lncRNAs) in adjusting mustard's drought stress response is largely unexplored. In this study, we showed that the drought-tolerant cultivar 'Weiliang' manifested a markedly lower base water potential (-1.073 MPa vs -0.437 MPa) and higher germination percentage (41.2% vs 0%) than the drought-susceptible cultivar 'Shuidong' under drought conditions. High throughput RNA sequencing techniques revealed a significant repertoire of lncRNAs from both cultivars during germination under drought stress, resulting in the identification of 2,087 differentially expressed lncRNAs (DELs) and their correspondingly linked 12,433 target genes. It was noted that 84 genes targeted by DEL exhibited enrichment in the photosynthesis pathway. Gene network construction showed that MSTRG.150397, a regulatory lncRNA, was inferred to potentially modulate key photosynthetic genes (Psb27, PetC, PetH, and PsbW), whilst MSTRG.107159 was indicated as an inhibitory regulator of six drought-responsive PIP genes. Further, weighted gene co-expression network analysis (WGCNA) corroborated the involvement of light intensity and stress response genes targeted by the identified DELs. The precision and regulatory impact of lncRNA were verified through qPCR. This study extends our knowledge of the regulatory mechanisms governing drought stress responses in mustard, which will help strategies to augment drought tolerance in this crop.


Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Germinación , Planta de la Mostaza , ARN Largo no Codificante , Planta de la Mostaza/genética , Germinación/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Estrés Fisiológico/genética , Semillas/genética , Semillas/crecimiento & desarrollo , ARN de Planta/genética , ARN de Planta/metabolismo , Redes Reguladoras de Genes
11.
Nat Commun ; 15(1): 5558, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977672

RESUMEN

Deletion of the maternal UBE3A allele causes Angelman syndrome (AS); because paternal UBE3A is epigenetically silenced by a long non-coding antisense (UBE3A-ATS) in neurons, this nearly eliminates UBE3A protein in the brain. Reactivating paternal UBE3A holds promise for treating AS. We previously showed topoisomerase inhibitors can reactivate paternal UBE3A, but their therapeutic challenges prompted our search for small molecule unsilencers with a different mechanism of action. Here, we found that (S)-PHA533533 acts through a novel mechanism to significantly increase paternal Ube3a mRNA and UBE3A protein levels while downregulating Ube3a-ATS in primary neurons derived from AS model mice. Furthermore, peripheral delivery of (S)-PHA533533 in AS model mice induces widespread neuronal UBE3A expression. Finally, we show that (S)-PHA533533 unsilences paternal UBE3A in AS patient-derived neurons, highlighting its translational potential. Our findings provide a lead for developing a small molecule treatment for AS that could be safe, non-invasively delivered, and capable of brain-wide unsilencing of paternal UBE3A.


Asunto(s)
Síndrome de Angelman , Modelos Animales de Enfermedad , Neuronas , Ubiquitina-Proteína Ligasas , Síndrome de Angelman/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Animales , Ratones , Neuronas/metabolismo , Humanos , Masculino , Femenino , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genética , Encéfalo/metabolismo
12.
Int J Mol Med ; 54(2)2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38963019

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly malignancy of the digestive tract. Recent research has identified long non­coding RNAs (lncRNAs) as crucial regulators in the pathogenesis of ESCC. These lncRNAs, typically exceeding 200 nucleotides, modulate gene expression through various mechanisms, including the competing endogenous RNA (ceRNA) pathway and RNA­protein interactions. The current study reviews the multifaceted roles of lncRNAs in ESCC, highlighting their involvement in processes such as proliferation, migration, invasion, epithelial­mesenchymal transition, cell cycle progression, resistance to radiotherapy and chemotherapy, glycolysis, apoptosis, angiogenesis, autophagy, tumor growth, metastasis and the maintenance of cancer stem cells. Specific lncRNAs like HLA complex P5, LINC00963 and non­coding repressor of NFAT have been shown to enhance resistance to radio­ and chemotherapy by modulating pathways such as AKT signaling and microRNA interaction, which promote cell survival and proliferation under therapeutic stress. Furthermore, lncRNAs like family with sequence similarity 83, member A antisense RNA 1, zinc finger NFX1­type containing 1 antisense RNA 1 and taurine upregulated gene 1 are implicated in enhancing invasive and proliferative capabilities of ESCC cells through the ceRNA mechanism, while interactions with RNA­binding proteins further influence cancer cell behavior. The comprehensive analysis underscores the potential of lncRNAs as biomarkers for prognosis and therapeutic targets in ESCC, suggesting avenues for future research focused on elucidating the detailed molecular mechanisms and clinical applications of lncRNAs in ESCC management.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , ARN Largo no Codificante/genética , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Animales , Transición Epitelial-Mesenquimal/genética , Proliferación Celular/genética
13.
COPD ; 21(1): 2363630, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38973373

RESUMEN

Chronic obstructive pulmonary disease (COPD) is preventable and requires early screening. The study aimed to examine the clinical values of long non-coding RNA (lncRNA) SNHG5 in COPD diagnosis and prognosis. Out of 160 COPD patients, 80 were in the stable stage and 80 were in the acute exacerbation of COPD stage (AECOPD). SNHG5 expression was detected via qRT-PCR. The survival analysis was conducted using Cox regression analysis and K-M curve. SNHG5 levels significantly reduced in both stable COPD and AECOPD groups compared with the control group, with AECOPD group recording the lowest values. SNHG5 levels were negatively correlated with GOLD stage. Serum SNHG5 can differentiate stable COPD patients from healthy individuals (AUC = 0.805), and can screen AECOPD from stable ones (AUC = 0.910). SNHG5 negatively influenced the release of inflammatory cytokines. For AECOPD patients, those with severe cough and wheezing dyspnea symptoms exhibited the lowest values of SNUG5. Among the 80 AECOPD patients, 16 cases died in the one-year follow-up, all of whom had low levels of SNHG5. SNHG5 levels independently influenced survival outcomes, patients with low SNHG5 levels had a poor prognosis. Thus, lncRNA SNHG5, which is downregulated in patients with COPD (especially AECOPD), can potentially protect against AECOPD and serve as a novel prognostic biomarker for AECOPD.


Asunto(s)
Progresión de la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica , ARN Largo no Codificante , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , ARN Largo no Codificante/genética , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Estudios de Casos y Controles , Citocinas/sangre , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Tos/etiología , Disnea/etiología , Biomarcadores/sangre , Relevancia Clínica
14.
Physiol Plant ; 176(4): e14424, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38973627

RESUMEN

Drought is one of the most common abiotic stresses that affect barley productivity. Long noncoding RNA (lncRNA) has been reported to be widely involved in abiotic stress, however, its function in the drought stress response in wild barley remains unclear. In this study, RNA sequencing was performed to identify differentially expressed lncRNAs (DElncRNA) among two wild barley and two cultivated barley genotypes. Then, the cis-regulatory networks were according to the chromosome position and the expression level correction. The GO annotation indicates that these cis-target genes are mainly involved in "ion transport transporter activity" and "metal ion transport transporter activity". Through weighted gene co-expression network analysis (WGCNA), 10 drought-related modules were identified to contract trans-regulatory networks. The KEGG annotation demonstrated that these trans-target genes were enriched for photosynthetic physiology, brassinosteroid biosynthesis, and flavonoid metabolism. In addition, we constructed the lncRNA-mediated ceRNA regulatory network by predicting the microRNA response elements (MREs). Furthermore, the expressions of lncRNAs were verified by RT-qPCR. Functional verification of a candidate lncRNA, MSTRG.32128, demonstrated its positive role in drought response and root growth and development regulation. Hormone content analysis provided insights into the regulatory mechanisms of MSTRG.32128 in root development, revealing its involvement in auxin and ethylene signal transduction pathways. These findings advance our understanding of lncRNA-mediated regulatory mechanisms in barley under drought stress. Our results will provide new insights into the functions of lncRNAs in barley responding to drought stress.


Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Hordeum , ARN Largo no Codificante , Estrés Fisiológico , Hordeum/genética , Hordeum/fisiología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Estrés Fisiológico/genética , Redes Reguladoras de Genes , ARN de Planta/genética
15.
J Cell Mol Med ; 28(13): e18496, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38984939

RESUMEN

Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as a novel therapeutic approach for HCC complexities. Moreover, while the interaction between long non-coding RNAs (lncRNAs) and mRNAs is pivotal in various physiological and pathological processes, their involvement in ferroptosis remains relatively unexplored. In this study, we constructed a ferroptosis-related lncRNA-mRNA correlation network in HCC using Pearson correlation analysis. Notably, the SLC7A11-AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed a significant correlation between the expression levels of this pair and key clinical characteristics of HCC patients, including gender, pathology, Ishak scores and tumour size. And poor prognosis was associated with high expression of this pair. Functional experiments demonstrated that SLC7A11-AS1, by binding to the 3'UTR region of SLC7A11 mRNA, enhanced its stability, thereby promoting HCC cell growth and resistance to erastin- induced ferroptosis. Additionally, in vivo studies confirmed that SLC7A11-AS1 knockdown potentiated the inhibitory effects of erastin on tumour growth. Overall, our findings suggest that targeting the SLC7A11-AS1/SLC7A11 pair holds promise as a potential therapeutic strategy for HCC patients.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Carcinoma Hepatocelular , Ferroptosis , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , ARN Largo no Codificante , Ferroptosis/genética , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Línea Celular Tumoral , Masculino , Femenino , Ratones , Pronóstico , Proliferación Celular/genética , Ratones Desnudos , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Piperazinas/farmacología
16.
J Cell Mol Med ; 28(13): e18527, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38984969

RESUMEN

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-ß signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-ß/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.


Asunto(s)
Epimedium , MicroARNs , Osteoblastos , ARN Largo no Codificante , Transducción de Señal , Proteína Smad2 , MicroARNs/genética , MicroARNs/metabolismo , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Proteína Smad2/metabolismo , Proteína Smad2/genética , Ratones , Epimedium/química , Transducción de Señal/efectos de los fármacos , Masculino , Regeneración Ósea/efectos de los fármacos , Humanos , Regulación de la Expresión Génica/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/genética
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 538-543, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38952094

RESUMEN

Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were collected from 25 UC patients and 25 healthy individuals at the General Hospital of Xizang Military Region. The expression levels of lncRNA H19 were detected, and the receiver operating characteristic (ROC) curve analysis was performed using serum samples. An in vitro inflammatory model was established in HT29 colorectal cells under lipopolysaccharide (LPS) stimulation, and the expression levels of lncRNA H19 were observed in HT29 cells through fluorescence quantitative PCR. HT29 cells with downregulated lncRNA H19 was constructed using lentivirus-mediated shRNA. The effect of lncRNA H19 on cell survival was analyzed through MTT assay. Cell apoptosis was detected by flow cytometry, and the protein expression levels of apoptosis and autophagy markers were analyzed through Western blot. After treatment with rapamycin, the survival of HT29 cells was observed by MTT assay. Results lncRNA H19 was highly expressed in the colonic mucosa and serum samples of UC patients with the ROC area being 0.786. Following LPS stimulation, the expression levels of lncRNA H19 was significantly increased in a time-dependent manner. Downregulation of lncRNA H19 can promote cell survival, inhibit cell apoptosis and increase autophagy level in HT29 cells. Treatment with rapamycin significantly increased the cell survival rate. Conclusion Knock-down of lncRNA H19 increases autophagy levels, inhibits LPS-induced apoptosis and promotes the survival of colon cells.


Asunto(s)
Apoptosis , Autofagia , Colitis Ulcerosa , Lipopolisacáridos , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Autofagia/efectos de los fármacos , Autofagia/genética , Lipopolisacáridos/farmacología , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Células HT29 , Masculino , Femenino , Persona de Mediana Edad , Adulto , Técnicas de Silenciamiento del Gen
18.
Oncol Res ; 32(7): 1185-1195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948024

RESUMEN

Background: Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood. Methods: Here, the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts. Results: We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients, whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis. Moreover, we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma. Conclusions: Our findings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.


Asunto(s)
Apoptosis , Autofagia , Proliferación Celular , Neoplasias Pulmonares , ARN Largo no Codificante , Complejo Correpresor Histona Desacetilasa y Sin3 , Humanos , ARN Largo no Codificante/genética , Autofagia/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Apoptosis/genética , Animales , Ratones , Complejo Correpresor Histona Desacetilasa y Sin3/genética , Proliferación Celular/genética , Línea Celular Tumoral , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Regulación Neoplásica de la Expresión Génica , Estabilidad Proteica , Silenciador del Gen , Oncogenes , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Oncol Res ; 32(7): 1221-1229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948025

RESUMEN

At present, the role of many long non-coding RNAs (lncRNAs) as tumor suppressors in the formation and development of cervical cancer (CC) has been studied. However, lncRNA prostate cancer gene expression marker 1 (PCGEM1), whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression, has not been studied in CC. The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC. The relative expression of PCGEM1 in CC cells was detected by real-time PCR. After the suppression of PCGEM1 expression by shRNA, the changes in the proliferation, migration, and invasion capacities were detected via CCK-8 assay, EdU assay, and colony formation assay wound healing assay. Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition (EMT) markers were determined by western blot and immunofluorescence. The interplay among PCGEM1, miR-642a-5p, and kinesin family member 5B (KIF5B) was confirmed by bioinformatics analyses and luciferase reporter assay. Results showed that PCGEM1 expressions were up-regulated within CC cells. Cell viabilities, migration, and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells. N-cadherin was silenced, but E-cadherin expression was elevated by sh-PCGEM1. Moreover, by sponging miR-642a-5p in CC, PCGEM1 was verified as a competitive endogenous RNA (ceRNA) that modulates KIF5B levels. MiR-642a-5p down-regulation partially rescued sh-PCGEM1's inhibitory effects on cell proliferation, migration, invasion, and EMT process. In conclusion, the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC. This study provides a research basis and new direction for targeted therapy of CC.


Asunto(s)
Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Cinesinas , MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Humanos , ARN Largo no Codificante/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , MicroARNs/genética , Femenino , Cinesinas/genética , Cinesinas/metabolismo , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Movimiento Celular/genética , Línea Celular Tumoral , Células HeLa , Invasividad Neoplásica
20.
Cell Mol Biol Lett ; 29(1): 93, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956502

RESUMEN

BACKGROUND: Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. METHODS: We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. RESULTS: We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. CONCLUSION: The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment.


Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Endometriales , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neovascularización Patológica , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neovascularización Patológica/genética , Femenino , Animales , Proliferación Celular/genética , Línea Celular Tumoral , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Movimiento Celular/genética , Ratones , Progresión de la Enfermedad , Ratones Desnudos , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Ratones Endogámicos BALB C , Pronóstico , Angiogénesis
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