舒尼替尼是转移性肾细胞癌的一线治疗药物，但其平均有效时间仅6-15个月，因此舒尼替尼的耐药机制是目前研究热点。通过建立细胞系和裸鼠两种舒尼替尼耐药模型，我们发现在耐药组中m6A修饰水平升高；m6A相关酶检测发现METTL14在耐药组中显著升高；敲低METTL14可降低m6A修饰水平并增加肾癌细胞对舒尼替尼的敏感性。m6A测序表明敲低METTL14后TRAF1的m6A修饰及表达水平均明显下降。因此我们提出假说：METTL14可通过对TRAF1的m6A修饰从而上调其表达，最终降低肾癌细胞对舒尼替尼的敏感性。本课题拟在现有研究基础上，通过一系列体内外实验，从细胞、动物多个层次研究METTL14在舒尼替尼耐药中的作用，为临床提高肾癌患者舒尼替尼的疗效提供新的思路。

Sunitinib is the first-line treatment for metastatic renal cell carcinoma (RCC), but most of the patients end up with drug resistance and tumor progression after 6–15 months of therapy. Thus, it is urgent to elucidate the underlying mechanisms of sunitinib resistance in RCC. By establishing sunitinib resistant cell lines and RCC xenografts models, we found that m6A level was higher in sunitinib resistant groups. Evaluation of m6A-related enzymes showed that METTL14 was significantly increased in resistant groups. Furthermore, knocking down METTL14 could decrease the m6A level and enhance the sensitivity of renal cancer cells to sunitinib. MeRIP-sequence showed that knocking down METTL14 could down-regulate both the m6A and expression level of TRAF1. Therefore, we hypothesized that METTL14 can up-regulate the expression of TRAF1 by m6A modification, and ultimately affect the susceptibility of renal cancer cells to sunitinib. On the basis of our previous studies, we plan to investigate the pivotal role of METTL14 in sunitinib resistance through in vivo and in vitro studies, thus providing new ideas and theories for RCC patients to improve the efficacy of Sunitinib