Identification of miR‐30c‐5p as a tumor suppressor by targeting the m6A reader HNRNPA2B1 in ovarian cancer. (18th October 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Cancer medicine. Volume 12:Number 4(2023)
• Page Start: 5055
• Page End: 5070
• Publication Date: 2022-10-18
• Subjects: Biological function -- HNRNPA2B1 -- m6A level -- miR‐30c‐5p -- ovarian cancer; 616.994005
• DOI: 10.1002/cam4.5246
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: microRNAs (miRNAs) and N6‐methyladenosine (m 6 A) play important roles in ovarian cancer (OvCa). However, the mechanisms by which miRNAs regulate m 6 A in OvCa have not been elucidated so far. Methods: To screen m 6 A‐related miRNAs, Pearson's correlation analysis of miRNAs and m 6 A regulators was implemented using The Cancer Genome Atlas database (TCGA). To determine the level of m 6 A, RNA m 6 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. Results: A total of 126 miRNAs were identified as m 6 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 m 6 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 m 6 A reader HNRNPA2B1 was highly expressed in OvCa tissues and related with poor prognosis. In vitro, knockdown of HNRNPA2B1 significantly reduced m 6 A level and hampered the proliferation and migration of OvCa cells. The inhibition of m 6 A reader HNRNPA2B1 attenuated the suppression of proliferation and migration and the low m 6 A level induced by the miR‐30c‐5p downregulation. Mechanistically, m 6 A reader HNRNPA2B1 might regulate CDK19 mRNA stability to alter m 6 A level. Conclusions: miR‐30c‐5p inhibits OvCa progression and reduces the m 6 A level by inhibiting m 6 A reader HNRNPA2B1, thus providing new insights into the m 6 A regulatory mechanism in OvCa. Abstract : miR‐30c‐5p inhibits OvCa progression by inhibiting m6A reader HNRNPA2B. Meanwhile, HNRNPA2B1 might regulate CDK19 mRNA stability to alter m6A level.