miR-200c与P-糖蛋白在胃癌中的表达及其临床意义、相关性以及对多药耐药的影响
Clinical significance and correlation of miR-200c and P-gp expression in gastric cancer and the effects on multidrug resistance.
作者信息
Wang Shen, Guo Jien, Mo Zhenzhou, Shi Xiangcheng, Qu Chongxiao
机构信息
Department of Gastrointestinal and Pancreatic Surgery, Shanxi Provincial People's Hospital, Taiyuan, China.
Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, China.
出版信息
J Gastrointest Oncol. 2022 Apr;13(2):581-592. doi: 10.21037/jgo-22-167.
BACKGROUND
Poor prognosis is common in gastric cancer patients due to multidrug resistance (MDR)-induced recurrence and metastasis. In the present study, we investigated the expression of microRNA (miR)-200c in gastric cancer tissues and cell lines and its relationship with the expression of the drug resistant gene which encodes P-glycoprotein (P-gp).
METHODS
The basic characteristics of 102 patients with gastric cancer were reviewed. Real time-polymerase chain reaction (PCR), immunohistochemistry, and Western blot were employed to detect the expression levels of miR-200c and P-gp in gastric carcinoma tissues and cell lines. The correlation of miR-200c messenger RNA (mRNA) level with clinicopathological characteristics and P-gp protein expression were analyzed. SGC7901/vincristine (VCR) cells were transfected with miR-200c mimics or a specific small interfering RNA (siRNA) targeting the gene. The methyl thiazolyl tetrazolium (MTT) assay and flow cytometry were used to determine the role of miR-200c and on the viability and apoptosis of gastric carcinoma cell lines.
RESULTS
The level of miR-200c in carcinoma tissues was significantly lower than that in adjacent tissues, and the expression level of P-gp in carcinoma tissues was obviously higher than that in adjacent tissues (P<0.01, P=0.029). The expression levels of miR-200c and P-gp were associated with the malignant characteristics of gastric cancer, and patients with high expression of miR-200c or negative expression of P-gp had a better prognosis (P=0.006, P=0.022). MiR-200c negatively regulated the gene in gastric cancer cell lines. MiR-200c overexpression and down-regulation increased the sensitivity of SGC7901/VCR cells to VCR and reversed MDR by promoting cell apoptosis.
CONCLUSIONS
The expression level of miR-200c decreases in gastric carcinoma tissues and drug-resistant gastric cancer SGC7901/VCR cells. Overexpression of miR-200c may enhance the sensitivity of SGC7901/VCR cells to VCR by regulating the expression of P-gp.
背景
由于多药耐药（MDR）导致的复发和转移，胃癌患者预后通常较差。在本研究中，我们调查了微小RNA（miR）-200c在胃癌组织和细胞系中的表达及其与编码P-糖蛋白（P-gp）的耐药基因表达的关系。
方法
回顾了102例胃癌患者的基本特征。采用实时聚合酶链反应（PCR）、免疫组织化学和蛋白质免疫印迹法检测miR-200c和P-gp在胃癌组织和细胞系中的表达水平。分析miR-200c信使核糖核酸（mRNA）水平与临床病理特征及P-gp蛋白表达的相关性。用miR-200c模拟物或靶向该基因的特异性小干扰RNA（siRNA）转染SGC7901/长春新碱（VCR）细胞。采用甲基噻唑基四氮唑（MTT）法和流式细胞术确定miR-200c和该基因对胃癌细胞系活力和凋亡的作用。
结果
癌组织中miR-200c水平显著低于癌旁组织，癌组织中P-gp表达水平明显高于癌旁组织（P<0.01，P=0.029）。miR-200c和P-gp的表达水平与胃癌的恶性特征相关，miR-200c高表达或P-gp阴性表达的患者预后较好（P=0.006，P=0.022）。miR-200c在胃癌细胞系中对该基因起负调控作用。miR-200c过表达和该基因下调可增加SGC7901/VCR细胞对VCR的敏感性，并通过促进细胞凋亡逆转MDR。
结论
miR-200c在胃癌组织和耐药胃癌SGC7901/VCR细胞中的表达水平降低。miR-200c过表达可能通过调节P-gp的表达增强SGC7901/VCR细胞对VCR的敏感性。
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