Zhu Feiya, Yang Tianru, Yao Mianfeng, Shen Ting, Fang Changyun
Department of Prosthodontics, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2021 Sep 23;11:716921. doi: 10.3389/fonc.2021.716921. eCollection 2021.
N6-methyladenosine (mA) modification is the most prevalent modification on eukaryotic RNA, and the mA modification regulators were involved in the progression of various cancers. However, the functions of mA regulators in oral squamous cell carcinoma (OSCC) remain poorly understood. In this study, we demonstrated that 13 of 19 mA-related genes in OSCC tissues are dysregulated, and HNRNPA2B1 was the most prognostically important locus of the 19 mA regulatory genes in OSCC. Moreover, HNRNPA2B1 expression is elevated in OSCC, and a high level of HNRNPA2B1 is significantly associated with poor overall survival in OSCC patients. Functional studies, combined with further analysis of the correlation between the expression of HNRNPA2B1 and the EMT-related markers from the TCGA database, reveal that silencing HNRNPA2B1 suppresses the proliferation, migration, and invasion of OSCC EMT. Collectively, our work shows that HNRNPA2B1 may have the potential to promote carcinogenesis of OSCC by targeting EMT the LINE-1/TGF-β1/Smad2/Slug signaling pathway and provide insight into the critical roles of HNRNPA2B1 in OSCC.
N6-甲基腺苷（mA）修饰是真核生物RNA中最普遍的修饰，且mA修饰调节因子参与了多种癌症的进展。然而，mA调节因子在口腔鳞状细胞癌（OSCC）中的功能仍知之甚少。在本研究中，我们证明了OSCC组织中19个与mA相关的基因中有13个表达失调，且HNRNPA2B1是OSCC中19个mA调节基因中预后最重要的位点。此外，HNRNPA2B1在OSCC中表达升高，高水平的HNRNPA2B1与OSCC患者较差的总生存期显著相关。功能研究结合对来自TCGA数据库的HNRNPA2B1表达与EMT相关标志物之间相关性的进一步分析表明，沉默HNRNPA2B1可抑制OSCC EMT的增殖、迁移和侵袭。总体而言，我们的工作表明，HNRNPA2B1可能通过靶向EMT的LINE-1/TGF-β1/Smad2/Slug信号通路促进OSCC的致癌作用，并为HNRNPA2B1在OSCC中的关键作用提供了见解。
