Modulation of IGF2BP1 by long non-coding RNA HCG11 suppresses apoptosis of hepatocellular carcinoma cells via MAPK signaling transduction.
Modulation of IGF2BP1 by long non-coding RNA HCG11 suppresses apoptosis of hepatocellular carcinoma cells via MAPK signaling transduction.
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长链非编码RNA HCG11调节IGF2BP1通过MAPK信号转导抑制肝癌细胞凋亡
DOI：
10.3892/ijo.2017.4066
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发表时间：
2017-09
影响因子：
5.2
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Xu Y;Zheng Y;Liu H;Li T
肝细胞癌是一种常见的肝脏恶性肿瘤。HCG11是一个长非编码家族的成员，我们前期的研究证实了HCG11在HCC中的上调。在本研究中，我们通过关注HCG11与其靶蛋白胰岛素样生长因子2 mrna结合蛋白1 （IGF2BP1）的相互作用来检测HCG11在HCC发展中的作用。HCG11和IGF2BP1的表达状况首次在临床HCC样本中进行研究。然后在人肝癌细胞系HepG2中抑制HCG11和IGF2BP1的表达，评估HepG2细胞的活力、增殖、凋亡和转移潜能。在分子水平上，我们还测定了p-ERK、p-JNK、p-p38、p21和cleaved caspase-3的表达水平，以解释HCG11在HCC进展中所涉及的功能途径。HCG11和IGF2BP1在HCC组织中的表达明显高于癌旁组织。敲低HCG11和IGF2BP1可导致HepG2细胞活力、增殖和迁移能力下降，而敲低HCG11和IGF2BP1可诱导细胞凋亡和G1细胞周期阻滞。此外，抑制HCG11和IGF2BP1的活性可阻断ERK、JNK和p38等抗凋亡因子的磷酸化，而激活p21和裂解caspase-3可启动HCC细胞的线粒体凋亡。HCG11通过与IGF2BP1相互作用，激活MAPK信号，最终促进HCC的发展。
Hepatocellular carcinoma (HCC) is a common malignancy of the liver. HCG11 is a member of long non-coding family, upregulation of which in HCC was proved by our previous study. In the present study, the role of HCG11 in the development of HCC was detected by focusing on the interaction between HCG11 and its target protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The expression status of HCG11 and IGF2BP1 was first investigated with clinical HCC samples. Then the expressions of HCG11 and IGF2BP1 were both inhibited in the human HCC cell line HepG2 and the cell viability, proliferation, apoptosis and metastasis potential of HepG2 cells were assessed. At molecular level, the expression levels of p-ERK, p-JNK, p-p38, p21 and cleaved caspase-3 were also determined to explain the pathways involved in the function of HCG11 in the progression of HCC. Expression of HCG11 and IGF2BP1 were significantly higher in HCC tissues than those in para-tumor tissues. Knockdown of both indicators led to decreased cell viability, proliferation, and migration ability in HepG2 cells while the cell apoptosis and G1 cell cycle arrest were induced after knockdown of HCG11 and IGF2BP1. In addition, suppressed activity of HCG11 and IGF2BP1 blocked the phosphorylation of anti-apoptosis factors, including ERK, JNK and p38 while the mitochondrial apoptosis in HCC cells was initiated by activation of p21 and cleaved caspase-3. HCG11 exerted its effect on HCC via interaction with IGF2BP1, leading to activation of MAPK signaling, which eventually promoted the progression of HCC.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5
作者：
Shi, Linxi;Peng, Fang;Li, Ning
通讯作者：
Li, Ning
影响因子：
10.5
作者：
BERNSTEIN, PL;HERRICK, DJ;ROSS, J
通讯作者：
ROSS, J
全面分析新型 microRNA-9 靶标以及 microRNA-9 通过靶向 IGF2BP1 在肝细胞癌中的肿瘤抑制作用
影响因子：
--
作者：
Zhang J;Cheng J;Zeng Z;Wang Y;Li X;Xie Q;Jia J;Yan Y;Guo Z;Gao J;Yao M;Chen X;Lu F
通讯作者：
Lu F
影响因子：
8
作者：
Bell, Jessica L.;Waechter, Kristin;Muehleck, Britta;Pazaitis, Nikolaos;Koehn, Marcel;Lederer, Marcell;Huettelmaier, Stefan
通讯作者：
Huettelmaier, Stefan