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GSG2 通过调节肝癌细胞增殖促进肿瘤生长。

GSG2 promotes tumor growth through regulating cell proliferation in hepatocellular carcinoma.

机构信息

Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, Henan, 450052, China.

出版信息

Biochem Biophys Res Commun. 2022 Oct 15;625:109-115. doi: 10.1016/j.bbrc.2022.07.093. Epub 2022 Jul 31.

DOI:10.1016/j.bbrc.2022.07.093
PMID:35952607
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant tumors in the world. In recent years, more and more inhibitors against gene targets have been found to be beneficial to survival. However, the function of homo-sapiens histone H3 associated protein kinase (GSG2) in HCC has not been completely understood.

METHODS

The expression of GSG2 in HCC tissues was detected by immunohistochemical staining. The lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown GSG2 expression in HCC cell lines Hep3B2.1-7 and SK-HEP-1. Cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively, and flow cytometry assay was used to investigate the cell apoptosis in vitro. Mice xenograft model was constructed to detect the functions of GSG2 on tumor growth in vivo. Human Apoptosis Antibody Array was conducted to find the possible mechanism.

RESULTS

GSG2 was overexpressed in HCC tissues compared with adjacent normal tissues. The knockdown of GSG2 had the functions of inhibiting the progression of HCC, including inhibiting cell proliferation and colony formation and promoting cell apoptosis. Compared with shCtrl group, the shGSG2 group expressed higher apoptotic genes such as caspase 3, caspase 8, Fas and FasL, while lower IGF1, Bcl2 and Bcl-w.

CONCLUSIONS

Our study showed that knockdown of GSG2 suppresses the tumor growth in vitro and vivo. Therefore, GSG2 might play an oncogenic role in HCC.

摘要

背景

肝细胞癌(HCC)是世界上最常见的诊断恶性肿瘤之一。近年来,越来越多的针对基因靶点的抑制剂被发现对生存有益。然而,人类组蛋白 H3 相关蛋白激酶(GSG2)在 HCC 中的功能尚未完全了解。

方法

通过免疫组织化学染色检测 HCC 组织中 GSG2 的表达。使用慢病毒介导的短发夹 RNA(shRNA)敲低 HCC 细胞系 Hep3B2.1-7 和 SK-HEP-1 中的 GSG2 表达。通过 MTT assay 和集落形成 assay 分别检测细胞增殖和集落形成,流式细胞术 assay 检测细胞凋亡。构建小鼠异种移植模型以检测 GSG2 在体内对肿瘤生长的作用。进行人细胞凋亡抗体阵列实验以寻找可能的机制。

结果

与相邻正常组织相比,GSG2 在 HCC 组织中过表达。敲低 GSG2 具有抑制 HCC 进展的功能,包括抑制细胞增殖和集落形成以及促进细胞凋亡。与 shCtrl 组相比,shGSG2 组表达更高的凋亡基因,如 caspase 3、caspase 8、Fas 和 FasL,而 IGF1、Bcl2 和 Bcl-w 表达较低。

结论

我们的研究表明,敲低 GSG2 抑制 HCC 的体内外肿瘤生长。因此,GSG2 可能在 HCC 中发挥致癌作用。

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