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Background: To systematically evaluate the relationship between the expression level of long noncoding RNA NEAT1 and the clinical characteristics and prognostic value of rectal cancer patients. Methods: PubMed, EMBASE, Cochrane library database and case-control studies on the correlation between abnormal expression of lncRNA NEAT1 and prognosis of rectal cancer patients published by the American clinical trials registry before May 1, 2023 were searched. The search time was from the establishment of the database to May 30, 2023. Results: A total of 7 case-control studies were included, including 1063 cancer patients. The results of meta-analysis showed that the high expression of lncRNA NEAT1 was significantly correlated with the degree of differentiation [or=0.45, 95%CI=0.32-0.63, P<0.01], tumor size [or=0.59, 95%CI=0.42-0.82, P<0.01], and overall survival [HR=1.34, 95%CI=1.21-1.48, P<0.001]; However, it was not associated with gender [or=1.23, 95%CI= 0.88-1.72, P=0.23] and lymph node metastasis [or=0.87, 95%CI=0.45-1.66, P=0.67]. Conclusions: The high expression of lncRNA NEAT1 may be a risk factor for poor prognosis in patients with malignant tumors, and lncRNA NEAT1 can be used as a potential biomarker to evaluate its prognosis.
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Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death.
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Péptidos y Proteínas de Señalización Intracelular , Neoplasias , Proteínas de Unión a Fosfato , Piroptosis , ARN no Traducido , Piroptosis/fisiología , Humanos , Neoplasias/patología , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , ARN no Traducido/genética , ARN no Traducido/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Animales , Regulación Neoplásica de la Expresión Génica , GasderminasRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is one of the most deadly cancers in the world. It usually has a bad prognosis and is challenging to identify in its early stages. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be important in the control of signaling pathways, cell behaviors, and epigenetic modification that contribute to the growth of tumors. The purpose of this work was to examine the relationship between CCA and lncRNA AL161431.1. METHODS: Using TCGA clinical survival data, we evaluated the association between AL161431.1 expression and patient prognosis. Using the program cluster Profiler R, enrichment analysis was performed. Additionally, the association between immune cell infiltration and AL161431.1 expression was evaluated by a review of the TCGA database. Next, to ascertain if AL161431.1 influences tumor growth, migration, and invasion in CCA, functional in vitro assays were conducted. Quantitative real-time polymerase chain reaction (qPCR) was employed to gauge AL161431.1 expression levels in CCA cells. Western blot was used to measure protein levels. RESULTS: In CCA, AL161431.1 was extremely expressed. The patients in the high-risk group had a significantly poorer overall survival (OS) than the patients in the low-risk group. A more thorough look at the TCGA data showed a relationship between high expression levels of AL161431.1 and increased infiltration of T cells, T helper cells, and NK CD56dim cells. Furthermore, AL161431.1 knockdown in CCA cells impeded invasion, migration, and proliferation and also lowered the expression of phosphorylated Smad2/Smad3 to restrain the TGFß/SMAD signaling pathway. CONCLUSIONS: Our results indicate that the lncRNA AL161431.1 activates the TGFß/SMAD signaling pathway to enhance CCA development and metastasis. AL161431.1 could be a novel target for cholangiocarcinoma treatment or a diagnostic marker.
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Neoplasias de los Conductos Biliares , Movimiento Celular , Colangiocarcinoma , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Colangiocarcinoma/metabolismo , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Técnicas de Silenciamiento del Gen , Pronóstico , Femenino , Masculino , Invasividad NeoplásicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment. AIM OF THE STUDY: To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments. MATERIALS AND METHODS: Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene. RESULTS: Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells. CONCLUSIONS: Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.
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Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.
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Hipoxia de la Célula , Redes Reguladoras de Genes , Células de Sertoli , Células de Sertoli/metabolismo , Animales , Masculino , Bovinos , Hipoxia de la Célula/genética , Transcriptoma , Perfilación de la Expresión Génica , ARN Largo no Codificante/genética , MicroARNs/genética , MicroARNs/metabolismo , Espermatogénesis/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Células Cultivadas , Regulación de la Expresión GénicaRESUMEN
AIMS: This study aimed to explore the effects of long noncoding RNA (lncRNA) H19 knockdown on angiogenesis and blood-brain barrier (BBB) integrity following cerebral ischemia/reperfusion (I/R) and elucidate their underlying regulatory mechanisms. METHODS: A middle cerebral artery occlusion/reperfusion model was used to induce cerebral I/R injury. The cerebral infarct volume and neurological impairment were assessed using 2,3,5-triphenyl-tetrazolium chloride staining and neurobehavioral tests, respectively. Relevant proteins were evaluated using western blotting and immunofluorescence staining. Additionally, a bioinformatics website was used to predict the potential target genes of lncRNA H19. Finally, a rescue experiment was conducted to confirm the potential mechanism. RESULTS: Silencing of H19 significantly decreased the cerebral infarct volume, enhanced the recovery of neurological function, mitigated BBB damage, and stimulated endothelial cell proliferation following ischemic stroke. Insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) is predicted to be a potential target gene for lncRNA H19. H19 knockdown increased IMP2 protein expression and IMP2 inhibition reversed the protective effects of H19 inhibition. CONCLUSION: Downregulation of H19 enhances angiogenesis and mitigates BBB damage by regulating IMP2, thereby alleviating cerebral I/R injury.
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Angiogénesis , Infarto de la Arteria Cerebral Media , Accidente Cerebrovascular Isquémico , ARN Largo no Codificante , Proteínas de Unión al ARN , Animales , Ratones , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Técnicas de Silenciamiento del Gen/métodos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/patología , Ratones Endogámicos C57BL , Neovascularización Fisiológica/fisiología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Modelos Animales de EnfermedadRESUMEN
TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.
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Long non-coding RNA LINC00908 is a functional biomarker in regulating tumour progression. Its dysregulation in gastric cancer implies its potential functional role. Few studies have noted the functional role of LINC00908 in gastric cancer. The potential of LINC00908 to serve as a biomarker in gastric cancer was evaluated. A total of 113 paired gastric cancer tissues and normal tissues were collected from patients with gastric cancer. LINC00908 levels were evaluated by polymerase chain reaction, and its significance in disease progression and patients' prognosis was assessed. In vitro, the function of LINC00908 in tumour-related cellular processes was evaluated with CCK8 and Transwell assay. Significant downregulation of LINC00908 was observed in gastric cancer and was negatively associated with disease development and overall survival of patients. LINC00908 showed significant inhibitory effects on the proliferation, migration, and invasion of gastric cancer cells. Additionally, miR-627-3p was sponged by LINC00908 and therefore mediated the function of LINC00908 in gastric cancer cells. LINC00908 functioned as a prognostic biomarker and tumour suppressor of gastric cancer, providing a therapeutic target for gastric cancer.
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Biomarcadores de Tumor , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , ARN Largo no Codificante/genética , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Proliferación Celular/genética , Movimiento Celular/genética , Línea Celular Tumoral , Anciano , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica/genéticaRESUMEN
BACKGROUND: Inflammatory cytokines such as Interleukin 1ß(IL1ß), IL6,Tumor Necrosis Factor-α (TNF-α) can inhibit osteoblast differentiation and induce osteoblast apoptosis. PANoptosis, a newly identified type of programmed cell death (PCD), may be influenced by long noncoding RNA (lncRNAs) which play important roles in regulating inflammation. However, the potential role of lncRNAs in inflammation and PANoptosis during osteogenic differentiation remains unclear. This study aimed to investigate the regulatory functions of lncRNAs in inflammation and apoptosis during osteogenic differentiation. METHODS AND RESULTS: High-throughput sequencing was used to identify differentially expressed genes involved in osteoblast differentiation under inflammatory conditions. Two lncRNAs associated with inflammation and PANoptosis during osteogenic differentiation were identified from sequencing data and Gene Expression Omnibus (GEO) databases. Their functionalities were analyzed using diverse bioinformatics methodologies, resulting in the construction of the lncRNA-miRNA-mRNA network. Among these, lncRNA (MIR17HG) showed a high correlation with PANoptosis. Bibliometric methods were employed to collect literature data on PANoptosis, and its components were inferred. PCR and Western Blotting experiments confirmed that lncRNA MIR17HG is related to PANoptosis in osteoblasts during inflammation. CONCLUSIONS: Our data suggest that TNF-α-induced inhibition of osteogenic differentiation and PANoptosis in MC3T3-E1 osteoblasts is associated with MIR17HG. These findings highlight the critical role of MIR17HG in the interplay between inflammation, PANoptosis, and osteogenic differentiation, suggesting potential therapeutic targets for conditions involving impaired bone formation and inflammatory responses.
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Diferenciación Celular , Redes Reguladoras de Genes , Osteogénesis , ARN Endógeno Competitivo , ARN Largo no Codificante , Factor de Necrosis Tumoral alfa , Animales , Humanos , Ratones , Apoptosis/genética , Diferenciación Celular/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/genética , MicroARNs/genética , MicroARNs/metabolismo , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Osteogénesis/genética , ARN Endógeno Competitivo/genética , ARN Endógeno Competitivo/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cadmium, a common metal pollutant, has been demonstrated to induce type 2 diabetes by disrupting pancreatic ß cells function. In this study, transcriptome microarray was utilized to identify differential gene expression in oxidative damage to pancreatic ß cells following cadmium exposure. The results indicated that a series of mRNAs, LncRNAs, and miRNAs were altered. Of the differentially expressed miRNAs, miR-29a-3p exhibited the most pronounced alteration, with an 11.62-fold increase relative to the control group. Following this, the target gene of miR-29a-3p was identified as Col3a1 through three databases (miRDB, miRTarbase and Tarbase), which demonstrated a decrease across the transcriptome microarray. The upstream target gene of miR-29a-3p was identified as NONMMUT036805, with decreased expression observed in the microarray. Finally, the expression trend of NONMMUT036805/miR-29a-3p/Col3a1 was reversed following NAC pretreatment. This was accompanied by a reduction in oxidative damage indicators, MDA/ROS/GSH-Px appeared to be negatively affected to varying degrees. In conclusion, this study has demonstrated that multiple RNAs are altered during cadmium exposure-induced oxidative damage in pancreatic ß cells. The NONMMUT036805/miR-29a-3p/Col3a1 axis has been shown to be involved in this process, which provides a foundation for the identification of potential targets for cadmium toxicity intervention.
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Cadmio , Células Secretoras de Insulina , MicroARNs , Estrés Oxidativo , ARN Endógeno Competitivo , Animales , Ratones , Cadmio/toxicidad , Línea Celular , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , ARN Endógeno Competitivo/genética , ARN Endógeno Competitivo/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , TranscriptomaRESUMEN
Coronary Slow Flow (CSF) is observed in individuals who experience delayed blood supply in the coronary arteries. Inflammation and endothelial dysfunction may play a role in the etiology and development of CSF. The current investigation aimed to compare the expression of specific long noncoding RNAs (lncRNAs) associated with endothelial dysfunction and inflammation in CSF patients. This caseâcontrol study enrolled 72 CSF patients and 71 healthy individuals. Blood samples were collected, and serum marker levels were measured. The expression levels of lncRNAs ANRIL, MALAT1, and LINC00305 in peripheral blood mononuclear cells (PBMCs) were assessed using real-time Polymerase Chain Reaction (PCR). All statistical analyses were performed using SPSS 22, with the significance level set at P < 0.05. The study revealed that the relative expression of MALAT1 and LINC00305 was significantly lower in the CSF group (p < 0.01), whereas ANRIL was expressed at higher levels (p < 0.0001). The areas under the ROC curves (AUCs) for MALAT1, LINC00305, and ANRIL were 0.64, 0.66, and 0.75, respectively. Notably, the expression level of LINC00305 exhibited an inverse correlation with CSF incidence (OR: 0.83, p: 0.008) in contrast to that of ANRIL (OR: 1.43, p < 0.0001). Additionally, compared to those in the control group, the average BMI, WBC, RBC, Hb, LDH, LDL, FBS, and percentage of neutrophils in the CSF group were significantly greater (p< 0.05). lncRNA ANRIL is upregulated in CSF patients, whereas MALAT1 and LINC00305 are downregulated. Dysregulation of ANRIL, MALAT1, and LINC00305 may serve as diagnostic and predictive factors for CSF leakage.
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Gastric cancer remains a significant health challenge despite advancements in diagnosis and treatment. Early detection is critical to reducing mortality, necessitating the investigation of molecular mechanisms underlying gastric cancer progression. This study focuses on BRD4 expression and its correlation with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed significant upregulation of BRD4 in gastric cancer tissues compared to normal tissues, correlating negatively with miR-26a-3p and positively with DLG5-AS1 and JMJD1C-AS1 lncRNAs. Quantitative RT-PCR confirmed these findings in 25 gastric cancer tissue samples and 25 normal samples. BRD4's overexpression was associated with reduced survival rates and older patient age. MiR-26a-3p, a known tumor suppressor, showed decreased expression in gastric cancer tissues, with ROC analysis suggesting it, alongside BRD4, as a potential diagnostic biomarker. Additionally, bioinformatics predicted miR-26a-3p's interaction with BRD4 mRNA. Upregulated lncRNAs DLG5-AS1 and JMJD1C-AS1 likely act as competing endogenous RNAs, sponging miR-26a-3p, thus promoting BRD4 dysregulation. These lncRNAs have not been previously studied in gastric cancer. The findings propose a novel BRD4/lncRNA/miRNA regulatory axis in gastric cancer, highlighting the potential of BRD4, DLG5-AS1, and JMJD1C-AS1 as biomarkers for early diagnosis. Further studies with larger sample sizes and in vivo and in vitro experiments are needed to elucidate this regulatory mechanism's role in gastric cancer progression.
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Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.
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NORSF is a nuclear long noncoding RNA (lncRNA) that contributes to the follicular atresia and restrains 17ß-estradiol (E2) release by granulosa cells (GCs). Importantly, it is also a potential candidate gene in the quantitative trait locus (QTLs) for sow fertility traits. We identified NORSF as a candidate (causal) gene affecting sow fertility traits. A novel G-A variant was discovered at -478 nt of the NORSF promoter and termed as g.-478G>A. Association analysis revealed that this variant was associated with sow fertility traits (e.g., the total number of piglets born, the total number of piglets born alive, and the number of healthy piglets). Mechanistically, the g.-478G>A variant reduced the binding activity of the NORSF promoter to its transcription activator regulatory factor X7 (RFX7), leading to decreased NORSF promoter activity and transcription levels in sow GCs (sGCs), and weakened inhibitory effects on the transcription of CYP19A1, which encodes a rate-limiting enzyme for E2 synthesis and E2 release by sGCs. In addition, RFX7 is transcriptionally activated by P53, which restrains E2 release from sGCs via the RFX7/NORSF/CYP19A1 pathway. These findings indicate that the lncRNA NORSF is a causal gene in QTLs for sow fertility traits and define the P53/NORSF/CYP19A1 pathway as a new signaling pathway affecting sow reproduction, which provides a new target for improving female fertility.
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BACKGROUND: Liaoning cashmere goat is recognized as a valuable genetic resource breed, with restrictions on genetic outflow in China. Hair follicle development in the cashmere goat is influenced by melatonin and long non-coding RNAs (lncRNAs). However, the role of lncRNAs in facilitating melatonin-promoted cashmere growth remains poorly understood. Previous studies have identified a new lncRNA, lncRNA018392, which is involved in the melatonin-promoted proliferation of cashmere skin fibroblasts. METHOD: Flow cytometry and CCK-8 assays confirmed that silencing lncRNA018392 negates the effects of melatonin on cell proliferation, and that proliferation was reduced when the gene CSF1R, located near lncRNA018392, was inhibited. Further investigation using a dual-luciferase reporter assay showed that lncRNA018392 could positively regulate the promoter of CSF1R. RESULTS: Results from RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq) revealed that lncRNA018392 interacts with the transcription factor SPI1, with CSF1R being a downstream target gene regulated by SPI1. This interaction was confirmed by ChIP-PCR, which demonstrated SPI1's binding to CSF1R. CONCLUSIONS: This study found that the melatonin-responsive lncRNA018392 accelerates the cell cycle and promotes cell proliferation by recruiting SPI1 to upregulate the expression of the neighboring gene CSF1R. These findings provide a theoretical foundation for elucidating the molecular mechanisms of cashmere growth and for the molecular breeding of cashmere goats.
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Proliferación Celular , Fibroblastos , Cabras , Melatonina , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cabras/genética , Fibroblastos/metabolismo , Proliferación Celular/genética , Melatonina/farmacología , Melatonina/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Piel/metabolismo , Piel/citología , Regulación hacia Arriba/genética , Regulación hacia Arriba/efectos de los fármacos , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Folículo Piloso/metabolismo , TransactivadoresRESUMEN
Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles (e.g., nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino)ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor.
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Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10-15 mol/L and 1.56 × 10-14 mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals.
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The Shitou goose, the largest meat-type goose breed, is an ideal model for offering insights into enhancing meat production efficiency through understanding its genetic regulation of muscle development. Here, through whole-transcriptomic analysis of embryonic leg muscles, we identified 847 differentially expressed genes (DEG), 244 differentially expressed lncRNAs (DEL), 37 differentially expressed circRNAs (DEC), and 84 differentially expressed miRNAs (DEM). Gene ontology (GO) analysis highlighted the significant enrichment of differentially expressed RNAs in muscle structure development, actin filament-based processes, and the actin cytoskeleton pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified pathways associated with the FoxO signaling pathway, AMPK signaling pathway, Wnt signaling pathway and calcium signaling pathway. Furthermore, we utilized Miranda, TargetScan, and miRDB to identify regulatory networks that involve interactions between lncRNA-mRNA, circRNA-mRNA, miRNA-mRNA, lncRNA-miRNA-mRNA, and circRNA-miRNA-mRNA, which regulated the growth and development of skeletal muscle. Notably, differentially expressed genes within the ceRNA network were most significantly enriched in the regulation of actin cytoskeletal organization. Additionally, a lncRNA/circRNA-miRNA-mRNA ceRNA network related to muscle growth and development was constructed based on protein-protein interaction (PPI) analysis and hub genes selection using Cytoscape. This further elucidated the regulatory roles of noncoding RNAs (ncRNA) in the formation of muscle fibers in Shitou goose. In summary, this study provides a valuable transcriptional regulatory network for goose muscle development laying the groundwork for further exploration of the molecular regulatory mechanisms underlying the excellent meat production performance of Shitou goose.
RESUMEN
Recent studies on the regulatory networks implicated in Alzheimer's disease (AD) evince long non-coding RNAs (lncRNAs) as crucial regulatory players, albeit a poor understanding of the mechanism. Analyzing differential gene expression in the RNA-seq data from the post-mortem AD brain hippocampus, we categorized a list of AD-dysregulated lncRNA transcripts into functionally similar communities based on their k-mer profiles. Using machine-learning-based algorithms, their subcellular localizations were mapped. We further explored the functional relevance of each community through AD-dysregulated miRNA, RNA-binding protein (RBP) interactors, and pathway enrichment analyses. Further investigation of the miRNA-lncRNA and RBP-lncRNA networks from each community revealed the top RBPs, miRNAs, and lncRNAs for each cluster. The experimental validation community yielded ELAVL4 and miR-16-5p as the predominant RBP and miRNA, respectively. Five lncRNAs emerged as the top-ranking candidates from the RBP/miRNA-lncRNA networks. Further analyses of these networks revealed the presence of multiple regulatory triads where the RBP-lncRNA interactions could be augmented by the enhanced miRNA-lncRNA interactions. Our results advance the understanding of the mechanism of lncRNA-mediated AD regulation through their interacting partners and demonstrate how these functionally segregated but overlapping regulatory networks can modulate the disease holistically.
Asunto(s)
Enfermedad de Alzheimer , Redes Reguladoras de Genes , MicroARNs , ARN Largo no Codificante , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteína 4 Similar a ELAV/metabolismo , Proteína 4 Similar a ELAV/genética , Hipocampo/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genéticaRESUMEN
OBJECTIVE: Since in the cancer setting, tumor cells may use cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to evade the immune system. This study aimed to identify CTLA-4-related long non-coding RNAs (lncRNAs) and assess their roles in lung adenocarcinoma (LUAD) development. METHODS: Clinical and genomic data were obtained from The Cancer Genome Atlas (TCGA), MSigDB and Gene Weaver. CTLA-4-related lncRNA-based gene signatures (CTLA4LncSigs) were identified using Cox regression, establishing a risk score model and an independent prognostic model. Enrichment analysis (GO/KEGG) was performed. Mendelian randomization (MR) analysis investigated the nitrogen metabolism and lung cancer relationship, with Bayesian weighted MR (BWMR) addressing uncertainties. Correlations with tumor microenvironment and drug sensitivity were explored. RESULTS: Nineteen CTLA4LncSigs significantly influenced LUAD prognosis. The risk score demonstrated independence as a prognostic factor. Functional analysis revealed lncRNAs' impact on nitrogen metabolism. MR and BWMR confirmed the protective role of the nitrogen metabolism pathway in lung cancer. CONCLUSION: Our study identifies CTLA-4-related lncRNAs associated with LUAD prognosis and uncovers a previously undiscovered protective role of the nitrogen metabolism pathway in combating LUAD development, providing new insights into potential therapeutic targets and prognostic biomarkers for this aggressive cancer subtype.