Sun Chun-Lei, Chen Jiong, Xing Zhi-Wei, Tao Gong-Shai
Cheeloo College of Medicine, Shandong University, Jinan, China.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China, 230001.
J Cancer. 2023 May 15;14(8):1407-1416. doi: 10.7150/jca.82158. eCollection 2023.
Cancer stem cell (CSC) characteristic contributes to tumor malignancy and progression. The role of N6-methyladenosine (m6A) modification in CSC characteristic is largely unknown. In this study, we found that m6A methyltransferase METTL14 was downregulated in colorectal cancer (CRC) and negatively correlated with the poor prognosis of CRC patients. Overexpression of METTL14 inhibited CSC characteristic, while knockdown of METTL14 promoted this characteristic. Through screening, NANOG was identified as the downstream of METTL14. Mechanically, we demonstrated that METTL14 inhibited cancer stem cell characteristic by regulating β-catenin. Collectively, our findings suggested that METTL16/β-catenin /NANOG axis might be promising therapeutic targets for CRC.
癌症干细胞（CSC）特性有助于肿瘤的恶性程度和进展。N6-甲基腺苷（m6A）修饰在CSC特性中的作用在很大程度上尚不清楚。在本研究中，我们发现m6A甲基转移酶METTL14在结直肠癌（CRC）中表达下调，且与CRC患者的不良预后呈负相关。METTL14的过表达抑制了CSC特性，而敲低METTL14则促进了这一特性。通过筛选，发现NANOG是METTL14的下游分子。机制上，我们证明METTL14通过调节β-连环蛋白来抑制癌症干细胞特性。总的来说，我们的研究结果表明METTL16/β-连环蛋白/NANOG轴可能是CRC有前景的治疗靶点。
