Liu Dongcheng, Li Wei, Zhong Fuhua, Yin Jianhua, Zhou Wei, Li Shixuan, Sun Xuefeng, Xu Jing, Li Guofeng, Wen Yuxin, Wang Jiaqing, Hong Malin, Cheng Zhiqiang, Yuan Jimin, Dai Lingyun, Sun Jichao, Wang Jigang, Qiu Chen, Wang Guangsuo, Zou Chang
Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, China.
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.
Front Pharmacol. 2020 Feb 28;11:178. doi: 10.3389/fphar.2020.00178. eCollection 2020.
Lung cancer remains a leading cause of cancer-associated mortality worldwide, however, molecular mechanisms underlying lung cancer tumorigenesis and progression remain unknown. Here, we report evidence showing that one member of the mammalian methyltransferase-like family (METTL), METTL7B, is a potential molecular target for treatment of non-small cell lung cancer (NSCLC). METTL7B expression was elevated in the majority of NSCLC comparing to normal tissues. Increased expression of METTL7B contributed to advanced stages of tumor development and poor survival in NSCLC patients. Lentivirus-mediated shRNA silencing of METTL7B suppressed proliferation and tumorigenesis of cancer cells and . Investigation on gene expression profiles of NSCLC cells revealed that abundant cell cycle related genes were downregulated in the absence of METTL7B. Pathway enrichment analysis indicated that METTL7B participated in cell cycle regulation. Notably, CCND1, a key regulator for G1/S transition, was significantly decreased with the depletion of METTL7B, resulting in G0/G1 arrest, indicating that METTL7B is critical for cell cycle progression. Taken together, our findings implicate that METTL7B is essential for NSCLC development and progression. METTL7B might serve as a potential therapeutic target for NSCLC.
肺癌仍然是全球癌症相关死亡的主要原因，然而，肺癌发生和发展的分子机制仍然未知。在此，我们报告证据表明，哺乳动物类甲基转移酶家族（METTL）的一个成员METTL7B是治疗非小细胞肺癌（NSCLC）的潜在分子靶点。与正常组织相比，大多数NSCLC中METTL7B的表达升高。METTL7B表达的增加导致肿瘤发展到晚期以及NSCLC患者生存率低下。慢病毒介导的METTL7B的shRNA沉默抑制了癌细胞的增殖和肿瘤发生。对NSCLC细胞基因表达谱的研究表明，在没有METTL7B的情况下，大量与细胞周期相关的基因被下调。通路富集分析表明METTL7B参与细胞周期调控。值得注意的是，作为G1/S转换关键调节因子的CCND1随着METTL7B的缺失而显著降低，导致G0/G1期阻滞，表明METTL7B对细胞周期进程至关重要。综上所述，我们的研究结果表明METTL7B对NSCLC的发生和发展至关重要。METTL7B可能作为NSCLC的潜在治疗靶点。
