HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer (CRC) is the second leading cause of cancer deaths, with approximately 15–25% of the primary diagnosis. MicroRNA-92a (miR-92a) is considered one of the most promising biomarkers for colorectal cancer diagnosis; however, at present the diagnostic accuracy of miR-92a for CRC remains inconclusive and the upstream regulatory mechanism is not well understood in CRC development. In this study, we firstly found that serum/plasma miR-92a had better diagnostic efficacy compared to stool samples in CRC through meta-analysis. Additionally, we confirmed that decreased miR-92a expression and secretion take place in CRC cells after knockdown of heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) in vitro. The common peaks of N6-methyladenosine (m6A) and HNRNPA2B1 in proximate miR-92a suggested HNRNPA2B1 mediated miR-92a expression through m6A modification. Thus, we identified that miR-92a derived from blood could be a better noninvasive biomarker, and provide insight into the mechanism of miR-92a in the expression and secretion in CRC. ABSTRACT: MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers, including colorectal cancer (CRC); however, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues, and this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence showed that knockdown of HNRNPA2B1 could significantly decrease miR-92a expression and secretion in RKO cells. HNRNPA2B1 mediated miR-92a via m6A RNA modification. These findings indicate that HNRNPA2B1-m6A RNA modification-derived MicroRNA-92a upregulation and section from the local CRC acts a candidate noninvasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis.