HNRNPA2B1 mediated MircoRNA-92a upregulation and section acts a promising non-invasive diagnostic biomarker in colorectal cancer

Background: 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. Method Diagnostic studies were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science, up until May 2022. Besides, an independent validation participants group (n = 144) was recruited for stool miR-92a test to prove the diagnosis efficiency in CRC. Then, totally studies were enrolled for meta-analysis using pooled sensitivity, specificity, and diagnostic odds ratios (DOR), summary receiver operating characteristic (SROC) curve and area under the curve (AUC) analysis. Next, GEO datasets, TCGA dataset and previous study data were used to explore the relationship between HRNPA2B1 and miR-92a. Finally, cell experiments demonstrated the regulatory effect of HRNPA2B1 on miR-92a in vitro. Results 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 shown that knockdown of HNRNPA2B1 could significantly decreased miR-92a expression and secretion in CRC cell lines. HNRNPA2B1 mediated miR-92a via with N6-methyladenosine (m6A) RNA modification validated by both bioinformatic analysis and vitro experiments. Conclusions These findings indicate that HNRNPA2B1-m6A RNA modification derived mircoRNA-92a upregulation and section from the local CRC acts a candidate non-invasive 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.