Liang Rong, Lin Yan, Yuan Chun-Ling, Liu Zhi-Hui, Li Yong-Qiang, Luo Xiao-Ling, Ye Jia-Zhou, Ye Hai-Hong
First Department of Chemotherapy, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, China.
Department of Hepatobilliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
Cell Prolif. 2017 Jun;50(3). doi: 10.1111/cpr.12340. Epub 2017 Mar 1.
Present evidence has suggested that large tumour suppressor 2 (LATS2) is abnormally expressed in most human cancer. However, the clinical and prognostic value in hepatocellular carcinoma (HCC) is still unknown.
Large tumour suppressor 2 mRNA and protein expression levels in HCC tissues and cell lines were detected by qRT-PCR, immunohistochemistry or Western blot. The correlation between LATS2 expression and clinicopathological factors was analysed through immunohistochemistry. The function of LATS2 on HCC cell growth and mobility was explored through MTT, colony formation, Transwell migration and invasion assays. The molecular mechanism of LATS2 was screened and confirmed by qRT-PCR and Western blot.
In this study, LATS2 mRNA and protein expressions were decreased in HCC tissues and cell lines compared with normal hepatic tissues and hepatic cell line. Low LATS2 expression was oppositely corrected with tumour stage, vascular invasion and metastasis. The univariate and multivariate analyses suggested that low LATS2 expression was an independent poor prognostic factor for HCC patients. The in vitro experiments showed that LATS2 regulated HCC cells migration and invasion, but had no effect on HCC cells proliferation. Meanwhile, LATS2 modulated metastasis-associated genes expression including E-cadherin, vimentin, snail, slug, MMP2 and MMP9. In conclusion, LATS2 is a prognostic biomarker and a tumour metastasis suppressor in HCC.
目前已有证据表明，大肿瘤抑制因子2（LATS2）在大多数人类癌症中表达异常。然而，其在肝细胞癌（HCC）中的临床及预后价值仍不明确。
采用qRT-PCR、免疫组织化学或蛋白质印迹法检测HCC组织及细胞系中LATS2 mRNA和蛋白表达水平。通过免疫组织化学分析LATS2表达与临床病理因素之间的相关性。通过MTT、集落形成、Transwell迁移和侵袭实验探讨LATS2对HCC细胞生长和迁移的作用。通过qRT-PCR和蛋白质印迹法筛选并确认LATS2的分子机制。
在本研究中，与正常肝组织和肝细胞系相比，HCC组织及细胞系中LATS2 mRNA和蛋白表达降低。LATS2低表达与肿瘤分期、血管侵犯及转移呈负相关。单因素和多因素分析表明，LATS2低表达是HCC患者独立的不良预后因素。体外实验表明，LATS2调控HCC细胞的迁移和侵袭，但对HCC细胞增殖无影响。同时，LATS2调节包括E-钙黏蛋白、波形蛋白、蜗牛蛋白、蛞蝓蛋白、基质金属蛋白酶2（MMP2）和基质金属蛋白酶9（MMP9）等转移相关基因的表达。总之，LATS2是HCC的预后生物标志物和肿瘤转移抑制因子。
