Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Exp Cell Res. 2018 Feb 15;363(2):235-242. doi: 10.1016/j.yexcr.2018.01.013. Epub 2018 Jan 10.
Increasing evidence has suggested that Capn4 is upregulated and functions as a potential tumor promoter in several human cancer types. However, the potential biological roles and regulatory mechanisms of Capn4 in colorectal cancer (CRC) remains unclear. Here, we found that Capn4 expression was elevated in CRC tissues than adjacent noncancerous tissues. Additionally, we also found that overexpression of Capn4 is significantly correlated with tumor progression and poor survival in CRC patients. Furthermore, our experimental data revealed that increased expression of Capn4 was observed in CRC cell lines and ectopic expression of Capn4 significantly enhanced in vitro cell proliferation, whereas knockdown of Capn4 suppressed CRC cells growth in vitro and in vivo. Moreover, our results indicate that Capn4 promotes cell proliferation by increasing MAPK7 expression, which has been reported to control the proliferation of many cancers. Mechanistically, Capn4 upregulates MAPK7 expression through activation of the Wnt/β-Catenin pathway in CRC cells. Therefore, we identified a tumorigenic role of Capn4 in CRC and suggested a potential therapeutic target for CRC patients.
越来越多的证据表明，Capn4 在几种人类癌症类型中上调并作为潜在的肿瘤促进因子发挥作用。然而，Capn4 在结直肠癌 (CRC) 中的潜在生物学作用和调节机制尚不清楚。在这里，我们发现 Capn4 在 CRC 组织中的表达水平高于相邻的非癌组织。此外，我们还发现 Capn4 的过表达与 CRC 患者的肿瘤进展和不良预后显著相关。此外，我们的实验数据显示，Capn4 在 CRC 细胞系中表达增加，异位表达 Capn4 显著增强体外细胞增殖，而 Capn4 的敲低则抑制体外和体内 CRC 细胞的生长。此外，我们的结果表明，Capn4 通过增加 MAPK7 的表达促进细胞增殖，MAPK7 的表达已被报道控制许多癌症的增殖。在机制上，Capn4 通过激活 CRC 细胞中的 Wnt/β-Catenin 通路上调 MAPK7 的表达。因此，我们鉴定了 Capn4 在 CRC 中的致癌作用，并为 CRC 患者提出了一个潜在的治疗靶点。
