Deng Biao, Fang JiaQing, Zhang XiaoFei, Qu Lei, Cao ZhongWei, Wang Bin
Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Gene. 2015 Oct 25;571(2):292-7. doi: 10.1016/j.gene.2015.06.083. Epub 2015 Jul 3.
Gelsolin (GSN), one of the most important actin structure regulating proteins, has been implicated in the oncogenesis of some cancers. In this study, we investigated the expression of GSN in hepatocellular carcinoma (HCC) and revealed its potential mechanisms. The mRNA and protein levels of GSN were overexpressed in HCC cells and HCC tissues compared to adjacent noncancerous tissues. GSN expression was correlated with venous invasion (P=0.0199) and Edmonson grading (P=0.0344) expression in HCC. Overexpression of GSN in Huh7 and SMMC-7721 cells significantly promoted cell proliferation and the number of Matrigel™-invading cells compared with control cells, with increased expression of matrix metalloproteinase MCL-1, MMP-2 and MMP-9, a key regulator of growth and invasion. In contrast, knockdown of GSN expression with small interfering RNA (siRNA) in MHCC-97L and MHCC-97H cell lines resulted in decreased cell viability and cell invasion. Our findings indicated that GSN expression promoted tumor-associated phenotypes by facilitating proliferative and invasive capacities of HCC cells, which might serve as a potential therapeutic target for HCC treatment.
凝溶胶蛋白(GSN)是最重要的肌动蛋白结构调节蛋白之一,与某些癌症的肿瘤发生有关。在本研究中,我们调查了GSN在肝细胞癌(HCC)中的表达,并揭示了其潜在机制。与相邻的非癌组织相比,GSN的mRNA和蛋白水平在HCC细胞和HCC组织中过表达。GSN表达与HCC中的静脉侵犯(P=0.0199)和Edmonson分级(P=0.0344)相关。与对照细胞相比,在Huh7和SMMC-7721细胞中过表达GSN显著促进细胞增殖和基质胶侵袭细胞数量,同时基质金属蛋白酶MCL-1、MMP-2和MMP-9(生长和侵袭的关键调节因子)的表达增加。相反,在MHCC-97L和MHCC-97H细胞系中用小干扰RNA(siRNA)敲低GSN表达导致细胞活力和细胞侵袭能力下降。我们的研究结果表明,GSN表达通过促进HCC细胞的增殖和侵袭能力来促进肿瘤相关表型,这可能作为HCC治疗的潜在治疗靶点。