RNA-binding motif protein 43 (RBM43) suppresses hepatocellular carcinoma progression through modulation of cyclin B1 expression
RNA-binding motif protein 43 (RBM43) suppresses hepatocellular carcinoma progression through modulation of cyclin B1 expression
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RNA 结合基序蛋白 43 (RBM43) 通过调节细胞周期蛋白 B1 表达抑制肝细胞癌进展
DOI：
10.1038/s41388-020-1380-7
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发表时间：
2020-07-06
期刊：
影响因子：
8
通讯作者：
Wu, Jiaxue
中科院分区：
文献类型：
--
作者：
Feng, Huan;Liu, Juan;Wu, Jiaxue
RNA结合蛋白在癌症进展过程中mRNA的转录后调节中起关键作用。在这里，我们发现RNA结合基序蛋白43（RBM 43）在人类肿瘤中显著下调，并且其低表达与HCC患者的不良预后相关。RBM 43的过表达抑制了培养中的细胞增殖并导致肿瘤异种移植物的生长停滞，而下调RBM 43则起相反的作用。我们还证明了RBM 43的过表达或敲低会影响肝癌细胞的细胞周期进程。RBM 43直接与Cyclin B1 mRNA的3 ' UTR结合并调控其表达。此外，在二乙基亚硝胺（DEN）-四氯化碳（CCl 4）处理后，Rbm 43的丢失促进小鼠肝癌的发生和HCC的发展。总之，我们的数据表明，RBM 43是一种肿瘤抑制因子，通过调节细胞周期蛋白B1的表达来控制细胞周期，这为RBM 43在HCC中特别重要提供了证据。
RNA-binding proteins play key roles in the posttranscriptional regulation of mRNA during cancer progression. Here, we show that RNA-binding motif protein 43 (RBM43) is significantly downregulated in human tumors, and its low expression is correlated with poor prognosis in patients with HCC. Overexpression of RBM43 suppressed cell proliferation in culture and resulted in the growth arrest of tumor xenografts, whereas downregulating RBM43 played an opposite role. We have also demonstrated that overexpression or knockdown of RBM43 affects the cell-cycle progression of liver cancer cells. Mechanistically, RBM43 directly associated with the 3 ' UTR of Cyclin B1 mRNA and regulated its expression. Moreover, loss ofRbm43in mice promoted liver carcinogenesis and HCC development after diethylnitrosamine (DEN)-carbon tetrachloride (CCl4) treatment. Taken together, our data indicate that RBM43 is a tumor suppressor that controls the cell cycle through modulation of Cyclin B1 expression, providing evidence that RBM43 is particularly important in HCC.