Jiao Taiwei, Li Yue, Gao Tong, Zhang Yining, Feng Mingliang, Liu Mengyuan, Zhou Huan, Sun Mingjun
Department of Gastroenterology and Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Tumour Biol. 2017 Mar;39(3):1010428317695027. doi: 10.1177/1010428317695027.
MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.
MTA3过表达与致癌作用有关。本研究的目的是探讨MTA3在人类结直肠癌及结直肠癌细胞中的临床意义和生物学作用。采用免疫组织化学方法检测80例结直肠癌组织中MTA3蛋白的表达。分析MTA3与临床因素之间的关系，结果显示51.25%（41/80）的癌症病例中MTA3过表达。MTA3过表达与晚期TNM分期（p = 0.0086）和Ki67指数（p = 0.001）之间存在显著相关性。我们在LoVo细胞中过表达MTA3，并在HCT15细胞中降低其表达。结果显示，MTA3促进癌细胞增殖、侵袭、迁移和细胞周期进程，并抑制5-氟尿嘧啶诱导的LoVo细胞系凋亡。在HCT15细胞系中降低MTA3表达则显示出相反效果。此外我们发现，MTA3正向调节包括细胞周期蛋白D1和细胞周期蛋白E在内的细胞周期蛋白，还上调Bcl2并下调Bax表达。此外，我们发现MTA3可通过上调Wnt靶蛋白激活Wnt信号通路。我们的结果表明，MTA3过表达促进结直肠癌的发生、发展和化疗耐药。MTA3可作为结直肠癌潜在的治疗靶点。
