Identification of miR-30c-5p as a tumor suppressor by targeting the m6 A reader HNRNPA2B1 in ovarian cancer

microRNAs (miRNAs) and N6-methyladenosine (m6 A) play important roles in ovarian cancer (OvCa). However, the mechanisms by which miRNAs regulate m6 A in OvCa have not been elucidated so far.

miR-30c-5p inhibits OvCa progression and reduces the m6 A level by inhibiting m6 A reader HNRNPA2B1, thus providing new insights into the m6 A regulatory mechanism in OvCa.

To screen m6 A-related miRNAs, Pearson's correlation analysis of miRNAs and m6 A regulators was implemented using The Cancer Genome Atlas database (TCGA). To determine the level of m6 A, RNA m6 A quantitative assays were used. Then, colony formation assays, EdU assays, wound healing assays, and Transwell assays were performed. The dual-luciferase reporter assay was used to confirm the miRNA target genes. Protein-protein interaction (PPI) analysis of the target genes was performed, and hub genes were discovered using the cytoHubba/Cytoscape software. The underlying molecular mechanisms were explored by bioinformatics and RNA stability assays.

A total of 126 miRNAs were identified as m6 A-related miRNAs by Pearson's correlation analysis. Among them, the high level of miR-30c-5p was associated with good prognosis in OvCa patients. In vitro, the miR-30c-5p agomir lowered the m6 A level and inhibited OvCa cell proliferation, migration, and invasion. The hub target genes of miR-30c-5p were identified as (i) XPO1, (ii) AGO1, (iii) HNRNPA2B1, of which m6 A reader HNRNPA2B1 was highly expressed in OvCa tissues and related with poor prognosis. In vitro, knockdown of HNRNPA2B1 significantly reduced m6 A level and hampered the proliferation and migration of OvCa cells. The inhibition of m6 A reader HNRNPA2B1 attenuated the suppression of proliferation and migration and the low m6 A level induced by the miR-30c-5p downregulation. Mechanistically, m6 A reader HNRNPA2B1 might regulate CDK19 mRNA stability to alter m6 A level. Conclusions: miR-30c-5p inhibits OvCa progression and reduces the m6 A level by inhibiting m6 A reader HNRNPA2B1, thus providing new insights into the m6 A regulatory mechanism in OvCa.