Gao Yuewen, Liu Zhaoyan, Ding Zhaohong, Hou Shicai, Li Jun, Jiang Kehua
Department of General Surgery, The People's Hospital of Rizhao City, Rizhao, Shandong 276800, P.R. China.
Department of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.
Oncol Lett. 2018 Apr;15(4):4781-4788. doi: 10.3892/ol.2018.7976. Epub 2018 Feb 7.
To investigate the effect of microRNA (miR)-155 on colon cancer chemoresistance to cisplatine and its mechanism. Reverse transcription quantitative polymerase chain reaction was used to measure the levels of miR-155 and forkhead box O3 (FOXO3) in colon cancer specimens and cell lines. Overexpression of miR-155 and miR-155 inhibitor were transfected into colon cancer cell lines to investigate its role of chemoresistance to cisplatin in colon cancer. MTS assays were used to analyse cell viability . tumor formation assays were performed in C57BL/6 wild type and miR-155 knockout mice (miR-155-/-). A luciferase reporter assay was used to measure the translation of FOXO3. Additionally, the expression of FOXO3 was detected by western blot analysis. It was identified that miR-155 was markedly upregulated in colon cancer tissue and cell lines. Overexpression of miR-155 enhanced colon cancer cell chemoresistance to cisplatin and tumorigenesis . In addition, overexpression of miR-155 was associated with decreased levels of FOXO3, primarily through inhibiting the expression of FOXO3 to increase colon cancer resistanec to cisplatin. The present study demonstrated that miR-155 increased colon cancer drug resistance and decreased FOXO3 expression and . This may provide a novel method for the treatment of drug-resistant colon cancer.
探讨微小RNA(miR)-155对结肠癌顺铂化疗耐药性的影响及其机制。采用逆转录定量聚合酶链反应检测结肠癌标本和细胞系中miR-155和叉头框O3(FOXO3)的水平。将miR-155过表达载体和miR-155抑制剂转染至结肠癌细胞系,以研究其在结肠癌顺铂化疗耐药中的作用。采用MTS法分析细胞活力。在C57BL/6野生型和miR-155基因敲除小鼠(miR-155-/-)中进行肿瘤形成实验。采用荧光素酶报告基因检测法检测FOXO3的翻译情况。此外,通过蛋白质免疫印迹分析检测FOXO3的表达。结果发现,miR-155在结肠癌组织和细胞系中显著上调。miR-155过表达增强了结肠癌细胞对顺铂的化疗耐药性和肿瘤发生能力。此外,miR-155过表达与FOXO3水平降低有关,主要是通过抑制FOXO3的表达来增加结肠癌对顺铂的耐药性。本研究表明,miR-155增加了结肠癌的耐药性并降低了FOXO3的表达。这可能为耐药性结肠癌的治疗提供一种新方法。