Pan Qiu-Zhong, Pan Ke, Weng De-Sheng, Zhao Jing-Jing, Zhang Xiao-Fei, Wang Dan-Dan, Lv Lin, Jiang Shan-Shan, Zheng Hai-Xia, Xia Jian-Chuan
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
Mol Carcinog. 2015 Aug;54(8):598-607. doi: 10.1002/mc.22126. Epub 2013 Dec 23.
Annexin A3 (ANXA3) has been found to play important roles in cancer progression, metastasis, and drug resistance; however, its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the expression level, clinical significance and biologic function of ANXA3 in HCC. Real-time quantitative reverse transcriptase-polymerase chain reaction, western blotting and immunohistochemical staining were used to examine ANXA3 expression levels in HCC tumor tissue, and its correlation with the clinicopathological features and prognosis of HCC patients was analyzed. The biological functions of ANXA3 in cell proliferation, migration, invasion, and resistance to chemotherapy were also investigated. ANXA3 expression was significantly increased in HCC tissues as compared with adjacent non-tumorous tissues. Elevated ANXA3 expression was associated with tumor size, number of lesions, tumor stage, and poor prognosis. In hepatoma cell lines, exogenous ANXA3 transduction promoted the tumorigenic activity and metastatic potential of tumor cells. Small interfering RNA silencing of ANXA3 inhibited these processes. In addition, in vitro and in vivo experiments revealed that ANXA3 overexpression enhanced resistance to chemotherapy. Taken together, our findings reveal that ANXA3 might play an important role in HCC progression and chemoresistance, and could serve as a novel prognostic marker and therapeutic target for HCC.
膜联蛋白A3(ANXA3)已被发现在癌症进展、转移和耐药性中发挥重要作用;然而,其在肝细胞癌(HCC)中的作用仍不清楚。在本研究中,我们调查了ANXA3在HCC中的表达水平、临床意义和生物学功能。采用实时定量逆转录-聚合酶链反应、蛋白质免疫印迹法和免疫组织化学染色检测HCC肿瘤组织中ANXA3的表达水平,并分析其与HCC患者临床病理特征及预后的相关性。还研究了ANXA3在细胞增殖、迁移、侵袭和化疗耐药中的生物学功能。与相邻的非肿瘤组织相比,HCC组织中ANXA3表达显著增加。ANXA3表达升高与肿瘤大小、病灶数量、肿瘤分期及预后不良相关。在肝癌细胞系中,外源性ANXA3转导促进了肿瘤细胞的致瘤活性和转移潜能。ANXA3的小干扰RNA沉默抑制了这些过程。此外,体外和体内实验表明,ANXA3过表达增强了化疗耐药性。综上所述,我们的研究结果表明,ANXA3可能在HCC进展和化疗耐药中发挥重要作用,并可作为HCC的一种新的预后标志物和治疗靶点。