Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Oncol Rep. 2019 Nov;42(5):1825-1832. doi: 10.3892/or.2019.7310. Epub 2019 Sep 12.
The aim of the present study was to investigate the role of miR‑203a‑3p in colorectal cancer (CRC) and identify the target gene of microRNA (miR)‑203a‑3p. A total of 59 sets of cancer tissues and corresponding adjacent non‑tumor tissues were collected from CRC patients (aged 31‑78 years) between October 2016 and May 2017. Total RNA extraction and reverse transcription‑quantitative polymerase chain reaction analysis, transfection assay, and Transwell and apoptosis assays, western blot analysis, a luciferase reporter assay and immunohistochemistry were performed. miR‑203a‑3p was found to be significantly downregulated in CRC tissues compared with adjacent normal tissues. The overexpression of miR‑203a‑3p was shown to inhibit the invasion and migration of human CRC SW480 and HT29 cells, and increase their apoptosis rates. Furthermore, miR‑203a‑3p downregulated the expression of thrombospondin 2 (THBS2) in SW480 and HT29 cells. It was also experimentally demonstrated that miR‑203a‑3p binds to the 3'‑untranslated region of THBS2, downregulating THBS2 expression and thereby inhibiting CRC progression and metastasis. The expression of miR‑203a‑3p, which serves a tumor‑suppressive role, in CRC tissues was significantly downregulated. As miR‑203a‑3p was determined to target THBS2 to inhibit CRC progression and metastasis; thus, miR‑203a‑3p may be considered as a potential novel approach to treating CRC.
本研究旨在探讨 miR-203a-3p 在结直肠癌(CRC)中的作用,并鉴定 microRNA(miR)-203a-3p 的靶基因。收集了 59 例 CRC 患者(年龄 31-78 岁)的 2016 年 10 月至 2017 年 5 月期间的癌组织和相应的相邻非肿瘤组织。进行了总 RNA 提取和逆转录定量聚合酶链反应分析、转染试验、Transwell 和凋亡试验、Western blot 分析、荧光素酶报告基因检测和免疫组织化学检测。与相邻正常组织相比,CRC 组织中 miR-203a-3p 的表达明显下调。miR-203a-3p 的过表达显示可抑制人 CRC SW480 和 HT29 细胞的侵袭和迁移,并增加其凋亡率。此外,miR-203a-3p 下调了 SW480 和 HT29 细胞中血小板反应蛋白 2(THBS2)的表达。实验还证实 miR-203a-3p 结合到 THBS2 的 3'非翻译区,下调 THBS2 表达,从而抑制 CRC 的进展和转移。在 CRC 组织中,miR-203a-3p 作为抑癌基因的表达明显下调。由于 miR-203a-3p 被确定为靶向 THBS2 以抑制 CRC 的进展和转移;因此,miR-203a-3p 可能被认为是治疗 CRC 的一种潜在新方法。