MiR-193b-5p and miR-374b-5p are aberrantly expressed in endometriosis and suppress endometrial cell migration in vitro
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ABSTRACT:
PROVIDER: PRJNA1174758 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31039926_1.fastq.gz | Fastqsanger.gz | |||
| SRR31039926_2.fastq.gz | Fastqsanger.gz | |||
| SRR31039927_1.fastq.gz | Fastqsanger.gz | |||
| SRR31039927_2.fastq.gz | Fastqsanger.gz | |||
| SRR31039928_1.fastq.gz | Fastqsanger.gz |
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Project description:Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. Here, we identified differentially expressed miRNAs in endometriosis and studied their functional role in the disease. (2) Methods: Endometrial tissue was collected from women with endometriosis (n=15) and non-endometriosis controls (n=17). Dysregulated miRNAs were identified through small RNA-sequencing, and their biological significance was explored by target gene prediction and pathway analysis. Selected miRNAs were examined in paired ectopic endometriomas and eutopic endometrium (n=10) using qRT-PCR. Their roles in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing on transfected cells and the endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in the eutopic endometrium of women with endometriosis compared to endometrial tissue from women without endometriosis. Pathway analysis indicated enrichment in cell migration and proliferation associated pathways. Further ex-vivo studies of miR-193b-5p and miR-374b-5p showed that both miRNAs were up-regulated in endometriomas. Overexpression of these two miRNAs in vitro inhibited cell migration and mRNA sequencing revealed several migration-related genes that are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration.
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Project description:(1) Background: Endometriosis is a prevalent gynecological disease affecting 1 out of 10 women of reproductive age. MicroRNAs (miRNAs) may play a role in endometriosis, though their exact function is unclear. In this study we aimed to identify differentially expressed miRNAs in endometriosis and study their functional role in the disease. (2) Methods: Endometrial tissue was collected from patients with endometriosis (n=15) and healthy controls (n=17). Dysregulated miR-NAs were identified through small RNA-sequencing, and their function were explored by target gene prediction and pathway analysis. Selected miRNAs were validated in a cohort of paired ec-topic endometriomas and eutopic endometrium (n=10) using RT-qPCR. Their role in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing of the miRNA-transfected cells and endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in eutopic endometrium from women with en-dometriosis. Pathway analysis indicated enrichment in cell migration and proliferation pathways. miR-193b-5p and miR-374b-5p, selected for validation, were up-regulated in endometrioma. Over-expression of these two miRNAs in-vitro inhibited cell migration and mRNA sequencing further revealed that several genes related to cell migration are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration.
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Project description:miR-193b-5p and miR-374b-5p Are Aberrantly Expressed in Endometriosis and Suppress Endometrial Cell Migration In Vitro
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Project description:Emerging evidence suggests that aberrantly expressed microRNAs (miRNAs) participate in endometriosis pathogenesis. Our previous miRNA microarray analysis revealed dysregulated expression of miR-1229-5p in eutopic endometrial stromal cells (ESCs) from ovarian endometriosis patients compared with healthy controls. However, the role and mechanism of miR-1229-5p in EMs remain unclear.
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Project description:MicroRNAs (miRNAs) have important roles in gene regulation. Dysregulation of miRNAs has been associated with tumorigenesis. Recent studies suggest miR-193b is a tumor suppressor gene. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 (CCND1) in melanoma. Now we demonstrate that miR-193b regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. miRNA microarray profiling revealed the miR-193b level in malignant melanomas was significantly downregulated compared to benign nevi, while a tissue microarray demonstrated overexpression of Mcl-1 in malignant melanoma. The Mcl-1 expressions were inversely correlated with the miR-193b levels in melanoma tissue samples, suggesting a potential regulatory role of miR-193b. Overexpression of miR-193b repressed Mcl-1 in melanoma cell lines. It is well known that Mcl-1 knockdown confers cell sensitivity to ABT-737, a small molecular inhibitor of Bcl-2, Bcl-XL and Bcl-w. We found miR-193b, through repressing Mcl-1 expression, could also sensitize melanoma cells that were refractory to ABT-737. Furthermore, miR-193b directly regulates Mcl-1 by targeting the 3â untranslated region (3âUTR) of Mcl-1 mRNA. Interestingly, miR-193b may recognize sequences on the 3âUTR that do not base pair with its seed region. In conclusion, our study suggests the downregulation of miR-193b could be an early event during melanoma progression, and demonstrates miR-193b directly regulates Mcl-1 by targeting both seed and seedless sequences of the 3â UTR. 15 primary melanoma samples, 8 metastatic melanomas and 8 benign nevi samples were profiled on Agilent miRNA array platform
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