GNAI1 Suppresses Tumor Cell Migration and Invasion and is Post-Transcriptionally Regulated by Mir-320a/c/d in Hepatocellular Carcinoma.
GNAI1 Suppresses Tumor Cell Migration and Invasion and is Post-Transcriptionally Regulated by Mir-320a/c/d in Hepatocellular Carcinoma.
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DOI：
10.7497/j.issn.2095-3941.2012.04.003
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发表时间：
2012-12
影响因子：
5.5
通讯作者：
He XH
中科院分区：
文献类型：
--
作者：
Yao J;Liang LH;Zhang Y;Ding J;Tian Q;Li JJ;He XH
目的探讨鸟嘌呤核苷酸结合蛋白G(i) α-1亚基（GNAI1）在肝细胞癌（HCC）中的作用及调控。采用qRT-PCR和免疫组化（IHC）染色检测GNAI1在HCC中的表达。用含GNAI1的慢病毒转导单元感染，建立了稳定表达GNAI1的Huh-7和SNU-387细胞。将靶向GNAI1的siRNA转染SMMC-7721细胞，降低GNAI1在HCC细胞中的表达。将Mir-320a/c/d模拟物转染SMMC-7721和SK-Hep-1细胞，采用Western blot检测GNAI1的表达。Transwell法检测Huh-7、SNU-387、SK-Hep-1和SMMC-7721细胞的迁移和侵袭。GNAI1蛋白在HCC样品中显著下调，但其mRNA水平未发生变化。GNAI1在体外可抑制肝癌细胞的迁移和侵袭。进一步研究表明，GNAI1是HCC细胞中miR-320a/c/d的靶点。Transwell实验表明，这些microrna能够促进体外肝癌细胞的迁移能力和侵袭性。GNAI1在HCC中下调，抑制HCC细胞的迁移和侵袭。这项研究首次探讨了GNAI1在癌症中的作用。miR-320a/c/d对GNAI1的调控为靶向肝癌转移提供了新的治疗途径。
To explore the role and regulation of guanine nucleotide-binding protein G(i), α-1 subunit (GNAI1) in hepatocellular carcinoma (HCC). Expression of GNAI1 in HCC samples was determined by qRT–PCR and immunohistochemical (IHC) staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAI1 was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. GNAI1 is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.