Liu Chao, Xia Yan, Jiang Wei, Liu Yinkun, Yu Long
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
Liver Cancer Institute, Fudan University, Shanghai 200032, P.R. China.
Oncol Rep. 2014 May;31(5):2043-8. doi: 10.3892/or.2014.3096. Epub 2014 Mar 19.
Autophagy is an evolutionarily conserved cellular process that degrades cytoplasmic materials through the lysosomal pathway. The deregulation of autophagy is associated with several diseases, particularly cancer. Hepatocellular carcinoma (HCC) is one of the most aggressive cancers with a poor prognosis. The expression of autophagy-related genes in HCC and their relationships with HCC are largely unknown. In the present study, we analyzed the expression of autophagy-related genes based on the Oncomine database and quantitative PCR of HCC and adjacent liver tissues. We found that the mRNA and protein expression of GABARAPL1 was significantly decreased in HCC tissues compared with their adjacent liver tissues. In HCC cancer cell lines, overexpression of GABARAPL1 inhibited cell growth, while knockdown of GABARAPL1 expression via siRNA promoted cell growth. In addition, we found a significant correlation of low GABARAPL1 expression with poor differentiation of HCC cells (P=0.018), and with the absence of tumor capsules (P=0.047). Kaplan-Meier survival analysis showed a significant association between low GABARAPL1 expression and poor prognosis of HCC patients (P=0.0094). Our data showed for the first time that GABARAPL1 expression is associated with poor prognosis of HCC patients.
自噬是一种进化上保守的细胞过程,通过溶酶体途径降解细胞质物质。自噬失调与多种疾病相关,尤其是癌症。肝细胞癌(HCC)是侵袭性最强、预后最差的癌症之一。HCC中自噬相关基因的表达及其与HCC的关系在很大程度上尚不清楚。在本研究中,我们基于Oncomine数据库以及HCC和癌旁肝组织的定量PCR分析了自噬相关基因的表达。我们发现,与癌旁肝组织相比,HCC组织中GABARAPL1的mRNA和蛋白表达显著降低。在HCC癌细胞系中,GABARAPL1的过表达抑制细胞生长,而通过siRNA敲低GABARAPL1表达则促进细胞生长。此外,我们发现GABARAPL1低表达与HCC细胞低分化(P = 0.018)以及无肿瘤包膜(P = 0.047)显著相关。Kaplan-Meier生存分析显示,GABARAPL1低表达与HCC患者预后不良显著相关(P = 0.0094)。我们的数据首次表明,GABARAPL1表达与HCC患者的不良预后相关。