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Hsa_circ_0009910: oncogenic circular RNA targets microRNA-145 in ovarian cancer cells.

ABSTRACT: Circular RNAs (circRNAs) correlate with cancer cell phenotypes. Particularly, circRNAs mediate the cancer process as microRNAs (miRNAs) sponges. This study was to ascertain the roles of hsa_circ_0009910 in phenotypic aspects of ovarian cancer cells. Mantel-Cox test was performed to analyze the correlation between hsa_circ_0009910 and survival outcomes of ovarian cancer. Minigene reporter was constructed and small interfering-RNA was designed for constructing hsa_circ_0009910-dysregulated and miR-145-upregulated cells identified by qRT-PCR. Proliferative and motile activities were monitored by CCK and Transwell. Western blot was applied for quantification of cyclin D1, CDK4, CDK6, MMP-2, MMP-9, IκBα, p65, Notch1, Hes1, and Hes5. miRNAs targets were predicted using a bioinformatics tool and confirmed using qRT-PCR and Dual-Luciferase reporter assay. Hsa_circ_0009910 was correlated with the poor prognosis of ovarian cancer patients. The ovarian cancer cell phenotypes were promoted by hsa_circ_0009910 while repressed by silencing hsa_circ_0009910. Hsa_circ_0009910 silence was responsible for the upregulation of the predicted miRNAs targets. Thereinto, miR-145 was confirmed as a miRNA target and negatively regulated by hsa_circ_0009910. miR-145 nullified the biological function of hsa_circ_0009910 in the proliferative and motile phenotypes, and the active status of NF-κB and Notch. Hsa_circ_0009910, representing unfavorable prognosis, induced proliferative and motile phenotypes by suppressing miR-145 in ovarian cancer cells.

SUBMITTER: Li Y

PROVIDER: S-EPMC7469526 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). Their interaction with disease-associated miRNAs indicates that circRNAs are important for the development of disease, and miR-145 has been previously shown to have antitumor effect in prostate cancer. In the current study, we successfully established the miR-145-overexpressed prostate cancer LNCaP cells (LNCaP-miR-145) using lentiviral vectors. LNCaP cells expressing the empty vector (LNCaP-NC) were used as the negative control. The circRNA expression in LNCaP-miR-145 cells was detected by microarray analysis, and the miRNA targets of circRNAs were predicted using the bioinformatics software TargetScan and miRanda. Quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of circRNAs in the prostate cancer tissue, nonmalignant tissue, LNCaP-miR-145 cells, and LNCaP-NC cells. The interaction of miRNA and circRNA was further confirmed by the dual-luciferase reporter assay. A total of 267 and 149 circRNAs were significantly up- and downregulated in LNCaP-miR-145 cells, respectively. hsa_circRNA_101981, hsa_circRNA_101996 and hsa_circRNA_09142 were the 3 circRNAs that interacted with hsa-miR-145-5p; hsa_circRNA_008068 and hsa_circRNA_406557 were the 2 circRNAs that interacted with hsa-miR-145-3p. Most of the circRNAs corresponded to the protein-coding exons. The expression levels of hsa_circRNA_101981, hsa_circRNA_00806, and hsa_circRNA_406557 were upregulated in the LNCaP-miR-145 cells, but downregulated in the prostate cancer tissue. In contrast, the expression levels of hsa_circRNA_101996 and hsa_circRNA_091420 were downregulated in the LNCaP-miR-145 cells, but upregulated in the prostate cancer tissue. Moreover, miR-145-5P might regulate the expression of hsa_circRNA_101981, hsa_circRNA_101996, and hsa_circRNA_09142, while miR-145-3P might regulate the expression of hsa_circRNA_008068 and hsa_circRNA_406557. Overexpression of miR-145 promoted the expression of hsa_circRNA_101981, hsa_circRNA_008068, and hsa_circRNA_406557 but suppressed the expressions of hsa_circRNA_101996 and hsa_circRNA_091420 in LNCaP cells. The results from the current study should give us a clue to clarify the tumor suppressive effect of miR-145.

Project description:BackgroundMicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis.ResultsThe expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context.ConclusionMiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in CRC provide a basis for understanding the functional role of miRNAs in cancer.

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Hsa_circ_0009910: oncogenic circular RNA targets microRNA-145 in ovarian cancer cells.

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