Shi Yu, Zheng Chunlei, Jin Yue, Bao Bowen, Wang Duo, Hou Kezuo, Feng Jing, Tang Shiying, Qu Xiujuan, Liu Yunpeng, Che Xiaofang, Teng Yuee
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Front Oncol. 2020 Jul 14;10:1126. doi: 10.3389/fonc.2020.01126. eCollection 2020.
The abnormal m6A modification caused by m6A modulators is a common feature of various tumors; however, little is known about which m6A modulator plays the most important role in triple-negative breast cancer (TNBC). In this study, when analyzing the influence of m6A modulators (, and ) on the prognosis of breast cancer, especially in TNBC using several on-line databases, methyltransferase-like 3 () was found to have low expression in breast cancer, and was closely associated with short-distance-metastasis-free survival in TNBC. Further investigation showed that knockdown of could enhance the ability of migration, invasion, and adhesion by decreasing m6A level in TNBC cell lines. Collagen type III alpha 1 chain () was identified and verified as a target gene of . could down-regulate the expression of by increasing its m6A methylation, ultimately inhibiting the metastasis of TNBC cells. Finally, with immunohistochemistry staining in breast cancer tissues, it was proved that expression was negatively correlated with in TNBC, but not in non-TNBC. This study demonstrated the potential mechanism of m6A modification in metastasis and provided potential targets for treatment in TNBC.
由m6A调节剂引起的异常m6A修饰是各种肿瘤的常见特征；然而，关于哪种m6A调节剂在三阴性乳腺癌（TNBC）中起最重要作用，人们知之甚少。在本研究中，当使用多个在线数据库分析m6A调节剂（、和）对乳腺癌预后的影响，特别是对TNBC的影响时，发现甲基转移酶样3（）在乳腺癌中表达较低，并且与TNBC的无远处转移生存期密切相关。进一步研究表明，敲低可通过降低TNBC细胞系中的m6A水平来增强迁移、侵袭和黏附能力。III型胶原蛋白α1链（）被鉴定并验证为的靶基因。可通过增加其m6A甲基化来下调的表达，最终抑制TNBC细胞的转移。最后，通过对乳腺癌组织进行免疫组化染色，证明在TNBC中表达与呈负相关，但在非TNBC中并非如此。本研究揭示了m6A修饰在转移中的潜在机制，并为TNBC的治疗提供了潜在靶点。
