Jiang Guiyang, Zhang Yong, Zhang Xiupeng, Fan Chuifeng, Wang Liang, Xu Hongtao, Yu Juanhan, Wang Enhua
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Tumour Biol. 2015 Nov;36(11):9005-13. doi: 10.1007/s13277-015-3664-z. Epub 2015 Jun 18.
Recent studies have implicated ARMc8 in promoting tumor formation in non-small cell lung cancer and breast cancer; however, so far, no studies have revealed the expression pattern or cellular function of ARMc8 in colon cancer. In this study, we used immunohistochemical staining to measure ARMc8 expression in 206 cases of colon cancer and matched adjacent normal colon tissue. Clinically important behaviors of cells, including invasiveness and migration, were evaluated after upregulation of ARMc8 expression in HT29 cells through gene transfection or downregulation of expression in LoVo cells using RNAi. We found that ARMc8 was primarily located in the membrane and cytoplasm of tumor cells, and its expression level was significantly higher in colon cancer in comparison to that in the adjacent normal colon tissues (p < 0.001). ARMc8 expression was closely related to TNM stage (p = 0.006), lymph node metastasis (p = 0.001), and poor prognosis (p = 0.002) of colon cancer. The invasiveness and migration capacity of HT29 cells transfected with ARMc8 were significantly greater than those of control cells (p < 0.001), while ARMc8 siRNA treatment significantly reduced cell invasion and migration in LoVo cells (p < 0.001). Furthermore, we demonstrated that ARMc8 could upregulate the expression of MMP7 and snail and downregulate the expression of p120ctn and α-catenin. Therefore, ARMc8 probably enhanced invasiveness and metastatic capacity by affecting these tumor-associated factors, thereby playing a role in enhancing the tumorigenicity of colon cancer cells. ARMc8 is likely to become a potential therapeutic target for colon cancer.
最近的研究表明,ARMc8在促进非小细胞肺癌和乳腺癌的肿瘤形成中起作用;然而,到目前为止,尚无研究揭示ARMc8在结肠癌中的表达模式或细胞功能。在本研究中,我们使用免疫组织化学染色法检测了206例结肠癌及配对的癌旁正常结肠组织中ARMc8的表达。通过基因转染上调HT29细胞中ARMc8的表达,或使用RNAi下调LoVo细胞中的表达后,评估了细胞的重要临床行为,包括侵袭性和迁移能力。我们发现,ARMc8主要位于肿瘤细胞的细胞膜和细胞质中,与癌旁正常结肠组织相比,其在结肠癌中的表达水平显著更高(p < 0.001)。ARMc8的表达与结肠癌的TNM分期(p = 0.006)、淋巴结转移(p = 0.001)及预后不良(p = 0.002)密切相关。转染ARMc8的HT29细胞的侵袭性和迁移能力显著高于对照细胞(p < 0.001),而ARMc8 siRNA处理显著降低了LoVo细胞的侵袭和迁移能力(p < 0.001)。此外,我们证明ARMc8可以上调MMP7和snail的表达,并下调p120ctn和α-catenin的表达。因此,ARMc8可能通过影响这些肿瘤相关因子增强侵袭性和转移能力,从而在增强结肠癌细胞的致瘤性中发挥作用。ARMc8可能成为结肠癌潜在的治疗靶点。