Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11

RBM15 的表观遗传激活通过调节 CXCL11 的 m6A 修饰促进透明细胞肾细胞癌的生长、转移和巨噬细胞浸润

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作者:Xing Zeng, Ke Chen, Le Li, Jihua Tian, Weiqiang Ruan, Zhiquan Hu, Dan Peng, Zhi Chen

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy that is characterized by poor prognosis. RNA-binding motif protein 15 (RBM15) has been identified as an oncogene in multiple tumors. Nevertheless, the function and mechanism of RBM15 in ccRCC are not clear. In this study, RBM15 was found to be upregulated in ccRCC cells and tissues. RBM15 enhanced the proliferation, clone formation, migration, invasion and epithelial-interstitial transition of ccRCC cells. Enhanced RBM15 was caused by the abundant histone 3 acetylation modification of the RBM15 promoter induced by EP300/CBP. RBM15 enhanced the stability of CXCL11 mRNA in an m6A-dependent manner. Moreover, RBM15 was found to promote macrophage infiltration and M2 polarization by promoting the secretion of CXCL11 in ccRCC cells in vitro and in vivo. Our findings highlight the function of RBM15 in ccRCC and reveal a novel identified EP300/CBP-RBM15-CXCL11 signaling axis, which promotes ccRCC progression and provides new insight into ccRCC therapy.

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