Identification of miR‐30c‐5p as a tumor suppressor by targeting the m6A reader HNRNPA2B1 in ovarian cancer

• Published in: Cancer medicine (Malden, MA) MA), 2023-02, Vol.12 (4), p.5055-5070
• Main Authors: Wu, Qiulei, Li, Guoqing, Gong, Lanqing, Cai, Jing, Chen, Le, Xu, Xiaohan, Liu, Xiaoli, Zhao, Jing, Zeng, Ya, Gao, Rui, Yu, Lili, Wang, Zehua
• Format: Article
• Language: English
• Subjects: Antibodies; Bioinformatics; Biological function; Cell growth; Cell migration; Cell proliferation; Chromosome 5; Correlation analysis; Datasets; DNA methylation; Epigenetics; Experiments; Gene expression; Genomes; HNRNPA2B1; m6A level; Medical research; MicroRNAs; miRNA; miR‐30c‐5p; Molecular modelling; mRNA stability; N6-methyladenosine; Ovarian cancer; Prognosis; Proteins; Tumor suppressor genes; Wound healing
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5246

Background microRNAs (miRNAs) and N6‐methyladenosine (m6A) play important roles in ovarian cancer (OvCa). However, the mechanisms by which miRNAs regulate m6A in OvCa have not been elucidated so far. Methods To screen m6A‐related miRNAs, Pearson's correlation analysis of miRNAs and m6A regulators was implemented using The Cancer Genome Atlas database (TCGA). To determine the level of m6A, RNA m6A 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. Results A total of 126 miRNAs were identified as m6A‐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 m6A 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 m6A reader HNRNPA2B1 was highly expressed in OvCa tissues and related with poor prognosis. In vitro, knockdown of HNRNPA2B1 significantly reduced m6A level and hampered the proliferation and migration of OvCa cells. The inhibition of m6A reader HNRNPA2B1 attenuated the suppression of proliferation and migration and the low m6A level induced by the miR‐30c‐5p downregulation. Mechanistically, m6A reader HNRNPA2B1 might regulate CDK19 mRNA stability to alter m6A level. Conclusions miR‐30c‐5p inhibits OvCa progression and reduces the m6A level by inhibiting m6A reader HNRNPA2B1, thus providing new insights into the m6A regulatory mechanism in OvCa. miR‐30c‐5p inhibits OvCa progression by inhibiting m6A reader HNRNPA2B. Meanwhile, HNRNPA2B1 might regulate CDK19 mRNA stability to alter m6A level.