RNA Binding Protein RNPC1 Inhibits Breast Cancer Cell Metastasis via Activating STARD13-Correlated ceRNA Network
RNA Binding Protein RNPC1 Inhibits Breast Cancer Cell Metastasis via Activating STARD13-Correlated ceRNA Network
复制标题
RNA 结合蛋白 RNPC1 通过激活 STARD13 相关 ceRNA 网络抑制乳腺癌细胞转移
DOI：
10.1021/acs.molpharmaceut.7b01123
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发表时间：
2018
影响因子：
4.9
通讯作者：
Xi Tao
中科院分区：
文献类型：
--
作者：
Zheng Lufeng;Zhang Zhiting;Zhang Shufang;Guo Qianqian;Zhang Feng;Gao Lanlan;Ni Haiwei;Guo Xinwei;Xiang Chenxi;Xi Tao
RNA结合蛋白（RBP）是转录后的重要调节因子。RNPC1是一种RBP，通过结合和调节癌细胞中靶基因的表达而发挥肿瘤抑制剂的作用。该研究揭示RNPC1表达与乳腺癌患者的无复发和总生存率正相关，并且RNPC1抑制乳腺癌细胞转移。从机制上讲，RNPC 1促进STARD13、CDH5、HOXD 10和HOXD 1之间的竞争性内源性RNA（ceRNA）网络串扰（STARD13相关的ceRNA网络），我们先前在乳腺癌细胞中通过稳定转录本并因此促进这四种基因在乳腺癌细胞中的表达证实了这一点。此外，RNPC1过表达抑制STARD13、CDH5、HOXD 10和HOXD 1敲低对细胞转移的促进作用。值得注意的是，RNPC1表达与乳腺癌组织中的CDH5、HOXD 1和HOXD 10表达呈正相关，并减弱了阿霉素耐药性。综上所述，这些结果确定RNPC 1可以通过促进STARD 13相关的ceRNA网络来抑制乳腺癌细胞转移。
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.