School of Life Science and Technology , China Pharmaceutical University , Nanjing 210009 , People's Republic of China.
Jiangsu Key Laboratory of Carcinogenesis and Intervention , China Pharmaceutical University , Nanjing 210009 , People's Republic of China.
Mol Pharm. 2018 Jun 4;15(6):2123-2132. doi: 10.1021/acs.molpharmaceut.7b01123. Epub 2018 May 15.
RNA binding proteins (RBPs) are pivotal post-transcriptional regulators. RNPC1, an RBP, acts as a tumor suppressor through binding and regulating the expression of target genes in cancer cells. This study disclosed that RNPC1 expression was positively correlated with breast cancer patients' relapse-free and overall survival and that RNPC1 suppressed breast cancer cell metastasis. Mechanistically, RNPC1 promotes competing endogenous RNA (ceRNA) network crosstalk among STARD13, CDH5, HOXD10, and HOXD1 (STARD13-correlated ceRNA network), which we previously confirmed in breast cancer cells through stabilizing the transcripts and thus facilitating the expression of these four genes in breast cancer cells. Furthermore, RNPC1 overexpression restrained the promotion of STARD13, CDH5, HOXD10, and HOXD1 knockdown on cell metastasis. Notably, RNPC1 expression was positively correlated with CDH5, HOXD1, and HOXD10 expression in breast cancer tissues and attenuated adriamycin resistance. Taken together, these results identified that RNPC1 could inhibit breast cancer cell metastasis via promoting a STARD13-correlated ceRNA network.
RNA 结合蛋白(RBPs)是至关重要的转录后调控因子。RNPC1 是一种 RBP,它通过与癌细胞中的靶基因结合并调节其表达来发挥肿瘤抑制作用。本研究表明,RNPC1 的表达与乳腺癌患者的无复发生存和总生存呈正相关,并且 RNPC1 抑制乳腺癌细胞转移。从机制上讲,RNPC1 促进了 STARD13、CDH5、HOXD10 和 HOXD1(STARD13 相关 ceRNA 网络)之间的竞争内源性 RNA(ceRNA)网络串扰,我们之前通过稳定这些转录本在乳腺癌细胞中证实了这一点,从而促进了这四个基因在乳腺癌细胞中的表达。此外,RNPC1 的过表达抑制了 STARD13、CDH5、HOXD10 和 HOXD1 敲低对细胞转移的促进作用。值得注意的是,在乳腺癌组织中,RNPC1 的表达与 CDH5、HOXD1 和 HOXD10 的表达呈正相关,并减弱了阿霉素耐药性。总之,这些结果表明,RNPC1 可以通过促进 STARD13 相关 ceRNA 网络来抑制乳腺癌细胞转移。