Department of Medicine Biotechnology, Medicine and Science Research Institute of Gansu Province, Lanzhou, China.
College of Life Sciences, Lanzhou University, Lanzhou, China.
BMC Cancer. 2018 Mar 27;18(1):344. doi: 10.1186/s12885-018-4285-x.
Reg IV is a member of the regenerating gene family and has been demonstrated to be overexpressed in gastric cancer. However, the functional mechanism of Reg IV in gastric cancer is still unclear.
Expression of Reg IV and SOX9 were investigated by immunohistochemistry (IHC) and real-time PCR, and the correlation between the expression of Reg IV and SOX9 was analyzed in gastric cancer tissues. Reg IV expression vectors and a siRNA of Reg IV and SOX9 were transfected into human gastric cancer cells and the protein and mRNA levels of Reg IV and SOX9 were investigated by western blot and real-time PCR. The invasion and migration ability of gastric cancer cells with overexpressed Reg IV and with gene silence of Reg IV and SOX9 were examined by transwell chambers and wound healing assay.
The Reg IV and SOX9 protein expression levels were both significantly higher in gastric cancer tissues compared with adjacent tissues (p = 0.022, p = 0.003). Reg IV protein expression significantly correlated with tumor invasion depth (p < 0.001), but had no significant correlations with age, clinical stage or lymph node metastasis. SOX9 protein expression also had no significant correlations with age, clinical stage, tumor invasion depth or lymph node metastasis. Reg IV transcript expression demonstrated a significant correlation with invasion depth and lymph node metastasis (p = 0.005, p < 0.001) and no significant correlations with age, clinical stage, tumor tissue differentiation or tumor size. SOX9 transcript expression demonstrated a significant correlation with invasion depth and tumor tissue differentiation (p = 0.044, p = 0.007) and no significant correlations with age, clinical stage or tumor size. The Reg IV expression showed a positive correlation with the SOX9 expression (p < 0.000, p = 0.008). Overexpression of Reg IV could upregulate SOX9 expression and promote invasiveness and migration of tumor cells, and silencing of Reg IV could downregulate SOX9 and inhibit invasiveness and migration of tumor cells in MKN-45 and AGS cells. On the other hand, silencing of SOX9 could upregulate Reg IV protein expression.
Our study demonstrated that Reg IV positively regulates the expression of SOX9 and is involved in tumor cell invasion and migration in gastric cancer.
Reg IV 是再生基因家族的成员，已被证明在胃癌中过表达。然而，Reg IV 在胃癌中的功能机制尚不清楚。
采用免疫组织化学（IHC）和实时 PCR 检测 Reg IV 和 SOX9 的表达，并分析胃癌组织中 Reg IV 和 SOX9 的表达相关性。转染人胃癌细胞的 Reg IV 表达载体和 Reg IV 和 SOX9 的 siRNA，通过 Western blot 和实时 PCR 检测 Reg IV 和 SOX9 的蛋白和 mRNA 水平。通过 Transwell 室和划痕愈合试验检测过表达 Reg IV 以及基因沉默的 Reg IV 和 SOX9 的胃癌细胞的侵袭和迁移能力。
Reg IV 和 SOX9 蛋白在胃癌组织中的表达均明显高于相邻组织（p=0.022，p=0.003）。Reg IV 蛋白表达与肿瘤浸润深度显著相关（p<0.001），但与年龄、临床分期或淋巴结转移无显著相关性。SOX9 蛋白表达与年龄、临床分期、肿瘤浸润深度或淋巴结转移均无显著相关性。Reg IV 转录物表达与浸润深度和淋巴结转移显著相关（p=0.005，p<0.001），与年龄、临床分期、肿瘤组织分化或肿瘤大小无显著相关性。SOX9 转录物表达与浸润深度和肿瘤组织分化显著相关（p=0.044，p=0.007），与年龄、临床分期或肿瘤大小无显著相关性。Reg IV 表达与 SOX9 表达呈正相关（p<0.000，p=0.008）。过表达 Reg IV 可上调 SOX9 表达并促进肿瘤细胞的侵袭和迁移，而沉默 Reg IV 可下调 MKN-45 和 AGS 细胞中肿瘤细胞的侵袭和迁移。另一方面，沉默 SOX9 可上调 Reg IV 蛋白表达。
本研究表明，Reg IV 正向调节 SOX9 的表达，并参与胃癌中肿瘤细胞的侵袭和迁移。
