Dong Xiang, Su Hailong, Jiang Feng, Li Haiyan, Shi Guangwen, Fan Lijuan
Digestive System Department, Jining First People's Hospital, Jining, Shandong 272011, P.R. China.
Department of General Surgery, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Oncol Lett. 2018 Jun;15(6):8311-8318. doi: 10.3892/ol.2018.8421. Epub 2018 Apr 4.
Gastric cancer has high incidence and mortality, and the mortality ranks second only to lung cancer. Downregulation of miR-133a has been observed in certain types of tumors, and it is involved in gastric cancer. The aim of the present study was to explore the molecular mechanisms of miR-133a and ubiquitin-specific protease 39 (USP39) in gastric cancer. Western blot analysis and RT-PCR were employed to measure miR-133a and USP39 expression. To confirm whether miR-133a targeted USP39, we conducted a luciferase reporter assay. We utilized 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay to detect the effects of miR-133a on gastric cell proliferation. miR-133a was significantly downregulated in cancer tissues and cell lines (HGC-27 and MGC-803), while the expression level of USP39 was higher in tumor tissues than in paracancerous tissues. Upregulated expression of miR-133a and/or USP39 downregulation could inhibit cell proliferation in gastric cancer cells. Furthermore, USP39 was identified as a direct target of miR-133a and the inverse relationship between them was also observed. USP39 was a firsthand target of miR-133a and there was a negative correlation between them. In addition, a low expression of miR-133a or overexpression of USP39 predicted poor prognosis. In conclusion, miR-133a may be a novel therapeutic target of microRNA-mediated suppression of cell proliferation in CC, but the role of the miR-133a/USP39 axis in CC progression needs further study.
胃癌具有高发病率和高死亡率，其死亡率仅次于肺癌。在某些类型的肿瘤中已观察到miR-133a的下调，并且它与胃癌有关。本研究的目的是探讨miR-133a和泛素特异性蛋白酶39（USP39）在胃癌中的分子机制。采用蛋白质免疫印迹分析和逆转录聚合酶链反应（RT-PCR）来检测miR-133a和USP39的表达。为了证实miR-133a是否靶向USP39，我们进行了荧光素酶报告基因检测。我们利用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四氮唑溴盐（MTT）检测法来检测miR-133a对胃细胞增殖的影响。miR-133a在癌组织和细胞系（HGC-27和MGC-803）中显著下调，而USP39在肿瘤组织中的表达水平高于癌旁组织。miR-133a表达上调和/或USP39表达下调可抑制胃癌细胞的增殖。此外，USP39被鉴定为miR-133a的直接靶点，并且还观察到它们之间的负相关关系。USP39是miR-133a的直接靶点，它们之间存在负相关。此外，miR-133a低表达或USP39过表达预示着预后不良。总之，miR-133a可能是微小RNA介导的抑制CC细胞增殖的新型治疗靶点，但miR-133a/USP39轴在CC进展中的作用需要进一步研究。
