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1.
Oncol Res ; 32(4): 643-658, 2024.
Article in English | MEDLINE | ID: mdl-38560570

ABSTRACT

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , MicroRNAs , Tumor Suppressor Proteins , Animals , Mice , Humans , Cisplatin/pharmacology , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice, Nude , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Apoptosis/genetics , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Autophagy/genetics , Gene Expression Regulation, Neoplastic , Nuclear Receptor Subfamily 1, Group F, Member 1/genetics , Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 1/pharmacology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Proto-Oncogene Proteins/genetics
2.
Cell Biochem Funct ; 42(3): e3996, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38561942

ABSTRACT

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.


Subject(s)
Adenine/analogs & derivatives , Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology
3.
Int J Rheum Dis ; 27(4): e15121, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562078

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. METHODS: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H-index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. RESULTS: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H-index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih-hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high-frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR-146a and miR-155. CONCLUSIONS: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR-146a and miR-155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration.


Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , MicroRNAs , Humans , MicroRNAs/genetics , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/genetics , Bibliometrics , Inflammation
4.
J Med Virol ; 96(4): e29571, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38563330

ABSTRACT

Persistent infection with high-risk human papillomavirus (HR-HPV) is a well-established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR-HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17ß-estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO-saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR-218 and the oncomiRNA miR-21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non-transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.


Subject(s)
Laurencia , MicroRNAs , Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Mice , Animals , Laurencia/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/drug therapy , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/pathology , MicroRNAs/genetics , Mice, Transgenic , Carcinogenesis , Papillomaviridae/genetics
5.
BMC Oral Health ; 24(1): 406, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38556858

ABSTRACT

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.


Subject(s)
Carcinoma, Squamous Cell , MicroRNAs , Tongue Neoplasms , Humans , Carcinoma, Squamous Cell/genetics , Prognosis , Tongue Neoplasms/genetics , Tongue Neoplasms/pathology , Biomarkers, Tumor/analysis , MicroRNAs/genetics , MicroRNAs/metabolism , Tongue/pathology
6.
BMC Cancer ; 24(1): 400, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561726

ABSTRACT

BACKGROUND: This study evaluated the clinical relevance of a set of five serum-derived circulating microRNAs (miRNAs) in colorectal cancer (CRC). Additionally, we investigated the role of miR-20a-5p released by exosomes derived from cancer-associated fibroblasts (CAFs) in the context of CRC. METHODS: The expression levels of five circulating serum-derived miRNAs (miR-20a-5p, miR-122-5p, miR-139-3p, miR-143-5p, and miR-193a-5p) were quantified by real-time quantitative PCR (RT-qPCR), and their associations with clinicopathological characteristics in CRC patients were assessed. The diagnostic accuracy of these miRNAs was determined through Receiver Operating Characteristic (ROC) curve analysis. CAFs and normal fibroblasts (NFs) were isolated from tissue samples, and subsequently, exosomes derived from these cells were isolated and meticulously characterized using electron microscopy and Western blotting. The cellular internalization of fluorescent-labeled exosomes was visualized by confocal microscopy. Gain- and loss-of-function experiments were conducted to elucidate the oncogenic role of miR-20a-5p transferred by exosomes derived from CAFs in CRC progression. The underlying mechanisms were uncovered through luciferase reporter assay, Western blotting, enzyme-linked immunosorbent assays, as well as proliferation and migration assays. RESULTS: The expression levels of serum-derived circulating miR-20a-5p and miR-122-5p were significantly higher in CRC and were positively correlated with advanced stages of tumorigenesis and lymph node metastasis (LNM). In contrast, circulating miR-139-3p, miR-143-5p, and miR-193a-5p were down-regulated in CRC and associated with early tumorigenesis. Except for miR-139-3p, they showed a negative correlation with LNM status. Among the candidate miRNAs, significantly elevated levels of miR-20a-5p were observed in both cellular and exosomal fractions of CAFs. Our findings indicated that miR-20a-5p induces the expression of EMT markers, partly by targeting PTEN. Exosomal miR-20a secreted by CAFs emerged as a key factor enhancing the proliferation and migration of CRC cells. The inhibition of miR-20a impaired the proliferative and migratory potential of CAF-derived exosomes in SW480 CRC cells, suggesting that the oncogenic effects of CAF-derived exosomes are mediated through the exosomal transfer of miR-20a. Furthermore, exosomes originating from CAFs induced increased nuclear translocation of the NF-kB p65 transcription factor in SW480 CRC cells, leading to increased interleukin-6 (IL-6) production. CONCLUSIONS: We established a set of five circulating miRNAs as a non-invasive biomarker for CRC diagnosis. Additionally, our findings shed light on the intricate mechanisms underpinning the oncogenic impacts of CAF-derived exosomes and underscore the pivotal role of miR-20a-5p in CRC progression.


Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Exosomes , MicroRNAs , Humans , Cancer-Associated Fibroblasts/metabolism , Carcinogenesis/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Exosomes/genetics , Exosomes/metabolism , Gene Expression Regulation, Neoplastic , Interleukin-6/genetics , Interleukin-6/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism
7.
J Transl Med ; 22(1): 323, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561750

ABSTRACT

BACKGROUND: MicroRNA (miRNA)-21-5p participates in various biological processes, including cancer and autoimmune diseases. However, its role in the development of fibrosis in the in vivo model of systemic sclerosis (SSc) has not been reported. This study investigated the effects of miRNA-21a-5p overexpression and inhibition on SSc fibrosis using a bleomycin-induced SSc mouse model. METHODS: A murine SSc model was induced by subcutaneously injecting 100 µg bleomycin dissolved in 0.9% NaCl into C57BL/6 mice daily for 5 weeks. On days 14, 21, and 28 from the start of bleomycin injection, 100 µg pre-miRNA-21a-5p or anti-miRNA-21a-5p in 1 mL saline was hydrodynamically injected into the mice. Fibrosis analysis was conducted in lung and skin tissues of SSc mice using hematoxylin and eosin as well as Masson's trichrome staining. Immunohistochemistry was used to examine the expression of inflammatory cytokines, phosphorylated signal transducer and activator of transcription-3 (STAT3) at Y705 or S727, and phosphatase and tensin homologue deleted on chromosome-10 (PTEN) in skin tissues of SSc mice. RESULTS: MiRNA-21a-5p overexpression promoted lung fibrosis in bleomycin-induced SSc mice, inducing infiltration of cells expressing TNF-α, IL-1ß, IL-6, or IL-17, along with STAT3 phosphorylated cells in the lesional skin. Conversely, anti-miRNA-21a-5p injection improved fibrosis in the lung and skin tissues of SSc mice, reducing the infiltration of cells secreting inflammatory cytokines in the skin tissue. In particular, it decreased STAT3-phosphorylated cell infiltration at Y705 and increased the infiltration of PTEN-expressing cells in the skin tissue of SSc mice. CONCLUSION: MiRNA-21a-5p promotes fibrosis in an in vivo murine SSc model, suggesting that its inhibition may be a therapeutic strategy for improving fibrosis in SSc.


Subject(s)
MicroRNAs , Scleroderma, Systemic , Animals , Mice , Bleomycin , Cytokines/metabolism , Disease Models, Animal , Fibrosis , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Scleroderma, Systemic/genetics , Scleroderma, Systemic/chemically induced , Skin/pathology
8.
Arch Virol ; 169(5): 88, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565755

ABSTRACT

Transcription of the covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is subject to dual regulation by host factors and viral proteins. MicroRNAs (miRNAs) can regulate the expression of target genes at the post-transcriptional level. Systematic investigation of miRNA expression in HBV infection and the interaction between HBV and miRNAs may deepen our understanding of the transcription mechanisms of HBV cccDNA, thereby providing opportunities for intervention. miRNA sequencing and real-time quantitative PCR (qRT-PCR) were used to analyze miRNA expression after HBV infection of cultured cells. Clinical samples were analyzed for miRNAs and HBV transcription-related indicators, using qRT-PCR, enzyme-linked immunoassay (ELISA), and Western blot. miRNA mimics or inhibitors were used to study their effects on the HBV life cycle. The target genes of miR-3188 and their roles in HBV cccDNA transcription were also identified. The expression of 10 miRNAs, including miR-3188, which was significantly decreased after HBV infection, was measured in clinical samples from patients with chronic HBV infection. Overexpression of miR-3188 inhibited HBV transcription, whereas inhibition of miR-3188 expression promoted HBV transcription. Further investigation confirmed that miR-3188 inhibited HBV transcription by targeting Bcl-2. miR-3188 is a key miRNA that regulates HBV transcription by targeting the host protein Bcl-2. This observation provides insights into the regulation of cccDNA transcription and suggests new targets for anti-HBV treatment.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , MicroRNAs , Humans , DNA, Circular/genetics , DNA, Viral/genetics , DNA, Viral/metabolism , Hepatitis B/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Viral Transcription , Virus Replication/genetics
9.
J Cell Mol Med ; 28(8): e18269, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38568056

ABSTRACT

Circular RNAs (circRNAs) play an important role in the progression of osteosarcoma. However, the precise function of circPVT1 in osteosarcoma remains elusive. This study aims to explore the molecular mechanism underlying the involvement of circPVT1 in osteosarcoma cells. We quantified circPVT1 expression using qRT-PCR in both control and osteosarcoma cell lines. To investigate the roles of circPVT1, miR-490-5p and HAVCR2 in vitro, we separately conducted overexpression and inhibition experiments for circPVT1, miR-490-5p and HAVCR2 in HOS and U2OS cells. Cell migration was assessed through wound healing and transwell migration assays, and invasion was measured via the Matrigel invasion assay. To elucidate the regulatory mechanism of circPVT1 in osteosarcoma, a comprehensive approach was employed, including fluorescence in situ hybridization, qRT-PCR, Western blot, bioinformatics, dual-luciferase reporter assay and rescue assay. CircPVT1 expression in osteosarcoma cell lines surpassed that in control cells. The depletion of circPVT1 resulted in a notable reduction in the in vitro migration and invasion of osteosarcoma cells. Mechanism experiments revealed that circPVT1 functioned as a miR-490-5p sequester, and directly targeted HAVCR2. Overexpression of miR-490-5p led to a significant attenuation of migration and invasion of osteosarcoma cells, whereas HAVCR2 overexpression had the opposite effect, promoting these abilities. Additionally, circPVT1 upregulated HAVCR2 expression via sequestering miR-490-5p, thereby orchestrating the migration and invasion in osteosarcoma cells. CircPVT1 orchestrates osteosarcoma migration and invasion by regulating the miR-490-5p/HAVCR2 axis, underscoring its potential as a promising therapeutic target for osteosarcoma.


Subject(s)
Bone Neoplasms , MicroRNAs , Osteosarcoma , Humans , In Situ Hybridization, Fluorescence , Cell Movement/genetics , Osteosarcoma/genetics , Bone Neoplasms/genetics , MicroRNAs/genetics , Hepatitis A Virus Cellular Receptor 2
10.
Arq Bras Cardiol ; 121(2): e20230462, 2024.
Article in Portuguese, English | MEDLINE | ID: mdl-38597542

ABSTRACT

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. OBJECTIVES: In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. METHODS: We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of |log2fold change| > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. RESULTS: 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. CONCLUSIONS: This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.


FUNDAMENTO: O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. OBJETIVOS: Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. MÉTODOS: Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de |log2fold change| > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. RESULTADOS: 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. CONCLUSÕES: Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.


Subject(s)
Coronary Artery Disease , MicroRNAs , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/genetics , Gene Expression Profiling/methods , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biomarkers , MicroRNAs/genetics , Transcription Factors/genetics , Computational Biology/methods , Inflammation
11.
Mol Biol Rep ; 51(1): 500, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598005

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.


Subject(s)
Inflammatory Bowel Diseases , MicroRNAs , RNA, Long Noncoding , Humans , Aged , RNA, Long Noncoding/genetics , Inflammatory Bowel Diseases/genetics , Inflammation/genetics , Glycoproteins , MicroRNAs/genetics , Biomarkers , Transforming Growth Factor beta/genetics
12.
Arch Dermatol Res ; 316(5): 118, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597990

ABSTRACT

Vitiligo, as a common pigment defect in the skin, hair, and mucous membranes, results from the destruction of melanocytes. Recent investigations have shown that miRNA dysregulation contributes in the pathogenesis of vitiligo. Therefore, in this research, our aim is to explore the relationship between miR-202 rs12355840, miR-211 rs8039189, and miR-1238 rs12973308 polymorphisms and susceptibility to vitiligo. A total number of 136 vitiligo patients and 129 healthy individuals as a control group were included in this research. The salting out approach was implemented to extraction genomic DNA. The genetic polymorphisms of miR-202 rs12355840, miR-211 rs8039189, and miR-1238 rs12973308 were determined using PCR-RFLP approach. The findings revealed that miR-202 rs12355840 polymorphism under codominant (CT and TT genotypes), dominant, recessive, overdominant, and also allelic models is correlated with increased risk of vitiligo. In addition, codominant, dominant, overdominant, as well as allelic models of miR-211 rs8039189 polymorphism decrease risk of vitiligo. No significant relationship was observed between the miR-1238 rs12973308 polymorphism and susceptibility to vitiligo. The miR-211 rs8039189 polymorphism may serve a protective effect on vitiligo development and miR-202 rs12355840 polymorphism may act as a risk factor for vitiligo susceptibility.


Subject(s)
MicroRNAs , Vitiligo , Humans , Vitiligo/epidemiology , Vitiligo/genetics , Polymorphism, Genetic , Skin , MicroRNAs/genetics , Polymorphism, Restriction Fragment Length
13.
Plant Mol Biol ; 114(3): 36, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598012

ABSTRACT

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.


Subject(s)
Arabidopsis , MicroRNAs , RNA, Long Noncoding , 60414 , RNA, Long Noncoding/genetics , Abscisic Acid/pharmacology , Arabidopsis/genetics , Mannitol , MicroRNAs/genetics , RNA, Messenger , Triticum/genetics , Waxes
14.
Immun Inflamm Dis ; 12(4): e1234, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38578001

ABSTRACT

BACKGROUND AND OBJECTIVE: Long noncoding RNAs (lncRNAs) are crucial in regulating various physiological and pathological processes, including immune responses. LINC01686 is a lncRNA with previously uncharacterized functions in immune regulation. This study aims to investigate the function of LINC01686 in lipopolysaccharide (LPS)-induced inflammatory responses in the human monocytic leukemia cell line THP-1 and its potential regulatory mechanisms involving miR-18a-5p and the anti-inflammatory protein A20. METHOD: THP-1 cells were stimulated with LPS to induce inflammatory responses, followed by analysis of LINC01686 expression levels. The role of LINC01686 in regulating the expression of interleukin (IL)-6, IL-8, A20, and signal transducer and activator of transcription 1 (STAT1) was examined using small interfering RNA-mediated knockdown. Additionally, the involvement of miR-18a-5p in LINC01686-mediated regulatory pathways was assessed by transfection with decoy RNAs mimicking the miR-18a-5p binding sites of LINC01686 or A20 messenger RNA. RESULTS: LINC01686 expression was upregulated in THP-1 cells following LPS stimulation. Suppression of LINC01686 enhanced LPS-induced expression of IL-6 and IL-8, mediated through increased production of reactive oxygen species. Moreover, LINC01686 knockdown upregulated the expression and activation of IκB-ζ, STAT1, and downregulated A20 expression. Transfection with decoy RNAs reversed the effects of LINC01686 suppression on A20, STAT1, IL-6, and IL-8 expression, highlighting the role of LINC01686 in sponging miR-18a-5p and regulating A20 expression. CONCLUSION: This study provides the first evidence that LINC01686 plays a critical role in modulating LPS-induced inflammatory responses in THP-1 cells by sponging miR-18a-5p, thereby regulating the expression and activation of A20 and STAT1. These findings shed light on the complex regulatory mechanisms involving lncRNAs in immune responses and offer potential therapeutic targets for inflammatory diseases.


Subject(s)
Cytokines , MicroRNAs , RNA, Long Noncoding , Humans , Cytokines/genetics , Cytokines/metabolism , Interleukin-6 , Interleukin-8/metabolism , Lipopolysaccharides , MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , THP-1 Cells
15.
FASEB J ; 38(7): e23598, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38581244

ABSTRACT

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non-coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high-sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT-PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR-136-3p and IGF2R in downstream processes, which was subsequently validated through qRT-PCR and dual-luciferase assays. Moreover, the inhibition of miR-136-3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR-136-3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.


Subject(s)
MicroRNAs , Female , Humans , Pregnancy , Apoptosis/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Fetal Growth Retardation/metabolism , In Situ Hybridization, Fluorescence , MicroRNAs/genetics , MicroRNAs/metabolism , Placenta/metabolism , Trophoblasts/metabolism
16.
Sci Rep ; 14(1): 8101, 2024 04 06.
Article in English | MEDLINE | ID: mdl-38582868

ABSTRACT

Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague-Dawley rats aged 2-3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1ß for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague-Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1ß-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.


Subject(s)
Cartilage, Articular , MicroRNAs , Osteoarthritis , Rats , Male , Animals , Hedgehog Proteins , MicroRNAs/genetics , MicroRNAs/therapeutic use , Rats, Sprague-Dawley , Matrix Metalloproteinase 13/genetics , Osteoarthritis/drug therapy , Osteoarthritis/genetics , Chondrocytes , Injections, Intra-Articular , Inflammation , Disease Models, Animal
17.
J Physiol Pharmacol ; 75(1)2024 02.
Article in English | MEDLINE | ID: mdl-38583436

ABSTRACT

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.


Subject(s)
Curcumin , Hominidae , MicroRNAs , Myocarditis , Pulmonary Embolism , Humans , Rats , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Curcumin/pharmacology , Curcumin/therapeutic use , Insulin Receptor Substrate Proteins/metabolism , Interleukin-6/metabolism , Apoptosis , Inflammation/drug therapy , Oxidative Stress , Pulmonary Embolism/drug therapy , Pulmonary Embolism/genetics , Hominidae/genetics , Hominidae/metabolism
18.
Int J Nanomedicine ; 19: 3143-3166, 2024.
Article in English | MEDLINE | ID: mdl-38585472

ABSTRACT

Background: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.


Subject(s)
Graphite , MicroRNAs , Nanocomposites , MicroRNAs/genetics , Osteogenesis/genetics , RNA, Circular , In Situ Hybridization, Fluorescence , Magnesium Oxide , Cells, Cultured , Bone Regeneration , Magnetic Phenomena , Cell Differentiation
19.
BMJ Open Diabetes Res Care ; 12(2)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38575156

ABSTRACT

INTRODUCTION: Diabetic kidney disease (DKD) is a major complication in patients with diabetes and the main contributor to the chronic kidney disease (CKD) global burden. Oxidative stress is a crucial factor in DKD pathogenesis but the role of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and its molecular regulators has been poorly investigated in man. RESEARCH DESIGN AND METHODS: In this case-control study, we analyzed the roles of Nrf2, a transcription factor shielding cells from oxidative stress, its repressor Kelch-like ECH-associated protein 1 (Keap1) and six microRNAs (miRNAs) that potentially suppress Nrf2. We categorized 99 participants into 3 groups: 33 non-dialysis patients with type 2 diabetes with DKD, 33 patients with type 2 diabetes without DKD and 33 control subjects and quantified the gene expression (messenger RNA (mRNA)) levels of Nrf2, Keap1 and 6 miRNAs. Moreover, we studied the correlation between gene expression levels and clinical indicators of kidney health. RESULTS: In patients with diabetes with DKD, Nrf2 mRNA levels were significantly lower than in patients without DKD (p=0.01) and controls (p=0.02), whereas no difference in Nrf2 expression levels existed between patients without DKD and controls. Conversely, in patients with and without DKD, Keap1 expression levels were significantly higher than in controls. Of the six miRNAs studied, miRNA 30e-5p showed differential expression, being markedly reduced in patients with DKD (p=0.007). Nrf2 mRNA levels directly correlated with estimated glomerular filtration rate (eGFR) in patients with DKD (r=0.34, p=0.05) and in a formal mediation analysis the eGFR emerged as the first factor in rank for explaining the difference in Nrf2 mRNA levels between patients with and without DKD. CONCLUSIONS: The observed dysregulation in the Nrf2-Keap1 axis and the unique expression pattern of miRNA30e-5p in DKD underscore the need for more focused research in this domain that can help identify novel intervention strategies for DKD in patients with type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , MicroRNAs , Humans , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Kidney/pathology , MicroRNAs/genetics , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , RNA, Messenger/genetics
20.
J Ovarian Res ; 17(1): 75, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575997

ABSTRACT

Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.


Subject(s)
Menopause, Premature , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , MicroRNAs , Primary Ovarian Insufficiency , Animals , Female , Mice , CD28 Antigens , Interleukin-10/genetics , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , Primary Ovarian Insufficiency/genetics , Primary Ovarian Insufficiency/therapy , Primary Ovarian Insufficiency/chemically induced , Proto-Oncogene Proteins c-akt
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