CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR
CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR
复制标题
CircBACH1 (hsa_circ_0061395) 通过 HuR 调节 p27 抑制促进肝细胞癌生长
DOI：
10.1002/jcp.29589
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发表时间：
2020-01-31
影响因子：
5.6
通讯作者：
Li, Jie
中科院分区：
文献类型：
--
作者：
Liu, Bingqi;Yang, Guangsheng;Li, Jie
近年来，在肝细胞癌（HCC）中发现了越来越多的环状RNA（circular RNA，circRNA）。然而，大多数circRNA的功能需要进一步研究。在这里，我们发现circBACH 1在HCC组织中显著上调，并且高circBACH 1水平与预后不良密切相关。此外，circBACH 1可以通过加速细胞周期进程在体外和体内促进HCC生长。我们接下来研究了细胞和分子机制，发现circBACH 1抑制p27翻译，从而影响细胞周期进程。此外，我们发现circBACH 1可以通过RNA免疫沉淀试验、下拉试验和电泳迁移率变化试验与HuR直接结合联合收割机。荧光原位杂交和免疫荧光结果表明，这些分子的结合促进了HuR从细胞核向细胞质的转位。最后，沉默HuR消除了circBACH 1对p27翻译的抑制，并消除了circBACH 1对HCC增殖的诱导作用。总之，circBACH 1作为癌基因通过circBACH 1/HuR/p27轴在HCC发展中发挥重要作用。
In recent years, an increasing number of circular RNAs (circRNAs) have been discovered in hepatocellular carcinoma (HCC). However, the functions of most circRNAs require further investigation. Here, we found that circBACH1 was significantly upregulated in HCC tissues and that high circBACH1 levels were closely associated with poor prognosis. In addition, circBACH1 could promote HCC growth by accelerating cell cycle progression in vitro and in vivo. We next investigated the cellular and molecular mechanisms and discovered that circBACH1 inhibited p27 translation, which influenced cell cycle progression. Moreover, we revealed that circBACH1 could combine directly with HuR using RNA immunoprecipitation assays, pull‐down assays, and electrophoretic mobility shift assays. The combination of these molecules facilitated HuR translocation from the nucleus to the cytoplasm according to the fluorescence in situ hybridization and immunofluorescence results. Finally, silencing HuR abrogated circBACH1's inhibition of p27 translation and abolished the circBACH1‐induced effect on HCC proliferation. In sum, circBACH1 plays a significant role as an oncogene through the circBACH1/HuR/p27 axis in HCC development.