HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

作者：Ke Li, Quan Gong, Xudong Xiang, Gang Guo, Jia Liu, Li Zhao, Jun Li, Nan Chen, Heng Li, Lijuan Zhang, Chun-Yan Zhou, Zhiyong Wang, Li Zhuang · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04190-8 · 被引用次数：67 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、MicroRNA in disease regulation

Abstract Background Accumulating data indicate that N6-methyladenosine (m 6 A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m 6 A “reader” has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m 6 A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC). Methods The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m 6 A modification of lncRNAs was screened by m 6 A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. Results We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in viv...