Wei Chen, Lei Liu, Hui Huang, Tao Zhang
Key Laboratory for Molecular Diagnosis of Hubei Province, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
Department of Gastrointestinal Surgery, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
Oncol Lett. 2019 Jul;18(1):856-863. doi: 10.3892/ol.2019.10358. Epub 2019 May 14.
An increasing number of studies have confirmed that miR-124 exhibits a suppressive role in glioblastoma, cervical cancer and breast cancer; however, the function of miR-124 in colorectal cancer (CRC) has not been completely elucidated. In the present study, miR-124 expression was confirmed by reverse transcription-quantitative PCR in 80 colorectal tissues and para-cancerous tissues. The influence of altered miR-124 expression was analyzed by statistical approaches including Cox multivariate regression analysis and the Kaplan-Meier method, and the target genes of miR-124 were confirmed by luciferase reporter assays. Immunohistochemical techniques were also performed in order to measure the expression levels of target proteins. miR-124 expression was observed to be decreased in colorectal tissue samples, and this phenomenon was correlated with adverse clinical indicators and poor patient survival time. Luciferase reporter assays indicated that miR-124 directly regulated TNF receptor associated factor 6 (TRAF6) 3'-untranslated region (UTR). Hence, it was proposed that miR-124 dysregulation may negatively influence the expression of TRAF6 and therefore serve as a biomarker of epithelial-mesenchymal transition in CRC tissues. In summary, the present study demonstrated that miR-124 regulates the expression of TRAF6, and may potentially function as an independent prognostic factor and therapeutic target in patients with CRC.
越来越多的研究证实，miR-124在胶质母细胞瘤、宫颈癌和乳腺癌中发挥抑制作用；然而，miR-124在结直肠癌（CRC）中的功能尚未完全阐明。在本研究中，通过逆转录定量PCR在80例结直肠组织和癌旁组织中证实了miR-124的表达。采用Cox多因素回归分析和Kaplan-Meier法等统计学方法分析miR-124表达改变的影响，并通过荧光素酶报告基因检测确定miR-124的靶基因。还进行了免疫组织化学技术以检测靶蛋白的表达水平。观察到结直肠组织样本中miR-124表达降低，且这种现象与不良临床指标和患者较差的生存时间相关。荧光素酶报告基因检测表明，miR-124直接调控肿瘤坏死因子受体相关因子6（TRAF6）的3'-非翻译区（UTR）。因此，有人提出miR-124失调可能对TRAF6的表达产生负面影响，因此可作为CRC组织上皮-间质转化的生物标志物。总之，本研究表明miR-124调节TRAF6的表达，并可能作为CRC患者独立的预后因素和治疗靶点。
