Dataset Information

Importance of Circ0009910 in colorectal cancer pathogenesis as a possible regulator of miR-145 and PEAK1.

ABSTRACT:

Introduction

Colorectal cancer (CRC) is one of the most frequent neoplasms in the world. Based on the emerging role of noncoding RNAs, particularly circular RNAs in pathogenesis of cancers, we designed this study to inspect the expression levels of a circ0009910-mediated regulatory pathway in colorectal cancer.

Methods

After bioinformatics analyses and construction of putative circ0009910/ miR-145-5p/PEAK1 pathway, the expression levels of these components were evaluated in 50 CRC tissues and adjacent specimens by quantitative real-time PCR. Moreover, we appraised the correlation coefficients between these transcripts and calculated the correlation between circ0009910 expression levels with clinicopathological features of patients.

Results

Circ0009910 and PEAK1 were significantly upregulated, while miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0009910, miR-145-5p, and PEAK1. We also reported considerable correlations between circ0009910 expression and clinicopathological parameters including sex and perineural invasion. Finally, ROC curve analysis showed circ0009910 level as a discriminative biomarker for CRC.

Conclusion

For the first time, we could introduce circ0009910 as an important biomarker in CRC. Collectively, this investigation helped us to identify a newly diagnosed pathway in CRC that can be a potential axis for designing effective drugs for treatment of CRC patients.

SUBMITTER: Kadkhoda S

PROVIDER: S-EPMC8417957 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: MicroRNAs (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. RESULTS: The 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. CONCLUSION: MiRNAs 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.