Pathology College, Qiqihar Medical University, Heilongjiang Province,161006, P. R. China.
Department of Endocrinology, the Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province,161000, P.R. China.
Cell Mol Biol (Noisy-le-grand). 2022 Sep 30;68(9):57-62. doi: 10.14715/cmb/2022.68.9.9.
This research was carried out to investigate the expression of miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins in colorectal adenocarcinoma and corresponding distal cutaneous normal mucosal tissues and their relationship with the clinicopathological parameters of colorectal adenocarcinoma as well as the correlation between miR-34a, miR-34b and PI3K/AKT/mTOR signaling pathway. The expression of p-PI3K, p-AKT, and mTOR proteins in 67 colorectal adenocarcinomas and the corresponding distal cut-off normal mucosa were assayed by immunohistochemistry. Their relationship with clinicopathological parameters and the correlation of the three proteins were evaluated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma and the corresponding distal cutaneous normal mucosa was detected by applying real-time quantitative PCR. The correlation between colorectal adenocarcinoma tissue miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins, respectively, was analyzed. Results showed that the expression of p-PI3K, p-AKT and mTOR proteins in colorectal adenocarcinoma tissues was higher than that in the corresponding distal cutaneous normal mucosa (P=0.000), and there was a positive correlation between the expression of the three proteins in colorectal adenocarcinoma tissues. The expression of p-PI3K and p-AKT protein in colorectal adenocarcinoma tissues were correlated with tumor size, differentiation degree, infiltration degree, lymph node metastasis and TNM stage (P<0.05). The expression of mTOR protein was related to tumor size and differentiation degree (P<0.05). The relative expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was less than that in the corresponding distal cutaneous normal mucosa (P<0.05), and the expression of miR-34a and miR-34b was positively correlated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was negatively correlated with the expression of p-PI3K, p-AKT and mTOR proteins. In conclusion, the PI3K/AKT/mTOR signaling pathway may promote colorectal adenocarcinoma and differentially participate in differentiation, infiltration and lymph node metastasis. Also, miR-34a and miR-34b may inhibit colorectal adenocarcinoma. Importantly, miR-34a and miR-34b may affect the development and progression of colorectal adenocarcinoma by regulating PI3K/AKT/mTOR signaling pathway.
本研究旨在探讨 miR-34a、miR-34b 及 p-PI3K、p-AKT、mTOR 蛋白在结直肠腺癌及相应远端皮肤正常黏膜组织中的表达及其与结直肠腺癌临床病理参数的关系，以及 miR-34a、miR-34b 与 PI3K/AKT/mTOR 信号通路的相关性。采用免疫组化法检测 67 例结直肠腺癌及相应远端截除正常黏膜组织中 p-PI3K、p-AKT、mTOR 蛋白的表达，评估其与临床病理参数的关系及三者蛋白的相关性。采用实时定量 PCR 检测结直肠腺癌及相应远端皮肤正常黏膜组织中 miR-34a、miR-34b 的表达，分析结直肠腺癌组织中 miR-34a、miR-34b 与 p-PI3K、p-AKT、mTOR 蛋白的相关性。结果显示，结直肠腺癌组织中 p-PI3K、p-AKT、mTOR 蛋白的表达高于相应远端皮肤正常黏膜组织（P=0.000），且结直肠腺癌组织中三者蛋白的表达呈正相关。结直肠腺癌组织中 p-PI3K、p-AKT 蛋白的表达与肿瘤大小、分化程度、浸润程度、淋巴结转移及 TNM 分期有关（P<0.05），mTOR 蛋白的表达与肿瘤大小及分化程度有关（P<0.05）。结直肠腺癌组织中 miR-34a、miR-34b 的相对表达量低于相应远端皮肤正常黏膜组织（P<0.05），且二者表达呈正相关。结直肠腺癌组织中 miR-34a、miR-34b 的表达与 p-PI3K、p-AKT、mTOR 蛋白的表达呈负相关。结论：PI3K/AKT/mTOR 信号通路可能促进结直肠腺癌的发生发展，并参与分化、浸润及淋巴结转移的差异表达。miR-34a、miR-34b 可能抑制结直肠腺癌的发生，通过调控 PI3K/AKT/mTOR 信号通路影响结直肠腺癌的发生发展。
