METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer
METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer
复制标题
METTL7B 是非小细胞肺癌中癌细胞增殖和肿瘤发生所必需的
DOI：
10.3389/fphar.2020.00178
复制
发表时间：
2020-02-28
影响因子：
5.6
通讯作者：
Zou, Chang
中科院分区：
文献类型：
--
作者：
Liu, Dongcheng;Li, Wei;Zou, Chang
肺癌仍然是全世界癌症相关死亡的主要原因，然而，肺癌肿瘤发生和进展的分子机制仍然未知。在此，我们报告的证据表明，哺乳动物甲基转移酶样家族 (METTL) 的成员之一 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 表达升高。 METTL7B 表达增加导致 NSCLC 患者肿瘤发展晚期和生存率低。慢病毒介导的 METTL7B shRNA 沉默可抑制体外和体内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 METTL7B 缺失的情况下，丰富的细胞周期相关基因被下调。通路富集分析表明METTL7B参与细胞周期调控。值得注意的是，CCND1（G1/S 转变的关键调节因子）随着 METTL7B 的消耗而显着减少，导致 G0/G1 停滞，表明 METTL7B 对于细胞周期进展至关重要。综上所述，我们的研究结果表明 METTL7B 对于 NSCLC 的发生和进展至关重要。 METTL7B 可能作为 NSCLC 的潜在治疗靶点。
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 in vitro and in vivo. 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.