Zhang Jing, Zhou Xingchun, Chang Hulin, Huang Xiaojun, Guo Xu, Du Xiaohong, Tian Siyuan, Wang Lexiao, Lyv Yinghua, Yuan Peng, Xing Jinliang
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Oncotarget. 2016 Oct 18;7(42):68976-68989. doi: 10.18632/oncotarget.12185.
Heat shock protein 60 (Hsp60), a typical mitochondrial chaperone, is associated with progression of various cancers. However, its expression and significance in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, the mRNA and protein expression of Hsp60 in HCC tissues were detected by quantitative RT-PCR (n=24), western blot (n=7), and immunohistochemical staining (n=295), respectively. The correlation between Hsp60 expression and clinicopathological characteristics of HCC patient was also analyzed. Meanwhile, the influence of Hsp60 on malignant phenotype of HCC cells was further investigated. We found that expression of Hsp60 was significantly downregulated in HCC tissues compared to peritumor tissues. Hsp60 expression was significantly correlated with serum alpha -foetoprotein (AFP) level and tumor differentiation grade. Moreover, high Hsp60 expression cancer/pericancer (C/P) ratio was associated with a better overall survival rate (P=0.035, n=295). The prognostic implication of Hsp60 in HCC was further confirmed in another cohort of 107 HCC patients (P=0.027). Up-regulation of Hsp60 remarkably induced the cell differentiation and inhibited the invasive potential of HCC in vitro and in vivo. Intriguingly, the down-regulation of Hsp60 significantly impaired mitochondrial biogenesis. Although more data are required to clarify the underling mechanism responsible for function of Hsp60, our results suggested that the effect of Hsp60 on differentiation and invasion of HCC cells might be associated with mitochondrial biogenesis. Collectively, our findings indicated that Hsp60 exerted a tumor suppressor function, and might serve as a potential therapeutic target in the treatment of HCC.
热休克蛋白60（Hsp60）是一种典型的线粒体伴侣蛋白，与多种癌症的进展相关。然而，其在肝细胞癌（HCC）中的表达及意义仍不清楚。在本研究中，分别采用定量逆转录聚合酶链反应（n = 24）、蛋白质免疫印迹法（n = 7）和免疫组织化学染色法（n = 295）检测Hsp60在肝癌组织中的mRNA和蛋白表达。同时分析Hsp60表达与肝癌患者临床病理特征之间的相关性。此外，进一步研究Hsp60对肝癌细胞恶性表型的影响。我们发现，与癌旁组织相比，Hsp60在肝癌组织中的表达显著下调。Hsp60表达与血清甲胎蛋白（AFP）水平及肿瘤分化程度显著相关。此外，高Hsp60表达的癌/癌旁（C/P）比值与更好的总生存率相关（P = 0.035，n = 295）。在另一组107例肝癌患者中，Hsp60在肝癌中的预后意义得到进一步证实（P = 0.027）。Hsp60的上调显著诱导细胞分化，并在体内外抑制肝癌的侵袭潜能。有趣的是，Hsp60的下调显著损害线粒体生物合成。尽管需要更多数据来阐明Hsp60功能的潜在机制，但我们的结果表明，Hsp60对肝癌细胞分化和侵袭的影响可能与线粒体生物合成有关。总之，我们的研究结果表明，Hsp60发挥肿瘤抑制功能，可能成为肝癌治疗的潜在靶点。
