Silencing of the TROP2 gene suppresses proliferation and invasion of hepatocellular carcinoma HepG2 cells

Silencing of the TROP2 gene suppresses proliferation and invasion of hepatocellular carcinoma HepG2 cells
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DOI:
10.1177/0300060518822913
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发表时间:
2019-03-01
影响因子:
1.6
通讯作者:
He, Zhenxing
He, Zhenxing
中科院分区:
医学4区
文献类型:
--
作者:
Zhang, Jian;Ma, Hai;He, Zhenxing

文献摘要

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目的观察到人滋养细胞表面抗原2 (Trop2)在多种肿瘤中的过表达;然而,其在肝细胞癌(HCC)的增殖、凋亡、迁移和侵袭中的作用尚不清楚。因此,本研究旨在表征Trop2在HCC中的功能。方法采用免疫组化方法检测肝癌组织中Trop2蛋白的表达。分别采用CCK-8、流式细胞术、Transwell和创面愈合试验检测细胞增殖、凋亡和侵袭。沉默Trop2基因后,用western blotting检测肝癌细胞系上皮-间充质转化相关蛋白和Trop2蛋白的表达水平。结果Trop2蛋白在肝癌组织和肝癌细胞系中高表达。转染Trop2 siRNA后,HepG2和HCCLM3细胞中Trop2 mRNA和蛋白表达水平下降。在HepG2和HCCLM3细胞中,沉默TROP2基因强烈抑制细胞增殖和迁移,同时促进细胞凋亡。分子机制研究表明,沉默TROP2基因可抑制HepG2和HCCLM3细胞的上皮-间质转化。结论本研究结果有助于进一步了解Trop2在调节细胞增殖和侵袭中的作用,并可能有助于开发新的HCC治疗方法。
Objectives Overexpression of human trophoblast cell surface antigen 2 (Trop2) has been observed in many cancers; however, its roles in proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) remain unclear. Thus, this study aimed to characterize the function of Trop2 in HCC. Methods Trop2 protein expression was detected by immunohistochemistry in HCC tissues. Cell proliferation, apoptosis, and invasion were respectively measured by CCK-8, flow cytometry, Transwell, and wound healing assays. Expression levels of epithelial-mesenchymal transition-related proteins and Trop2 protein in HCC cell lines were detected by western blotting after silencing of the TROP2 gene. Results Trop2 protein was highly expressed in HCC tissues and HCC cell lines. Trop2 mRNA and protein expression levels decreased in HepG2 and HCCLM3 cells after transfection with Trop2 siRNA. Silencing of the TROP2 gene in HepG2 and HCCLM3 cells strongly inhibited cell proliferation and migration, while enhancing cell apoptosis. Investigation of the molecular mechanism revealed that silencing of the TROP2 gene suppressed epithelial-mesenchymal transition of HepG2 and HCCLM3 cells. Conclusions The results of the present study may improve understanding of the role of Trop2 in regulation of cell proliferation and invasion, and may aid in development of novel therapy for HCC.