Department of General Surgery, Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Department of General Surgery, The First Affiliated Hospital, Xingtai Medical College, Xingtai, Hebei 054001, P.R. China.
Oncol Rep. 2018 Sep;40(3):1370-1378. doi: 10.3892/or.2018.6524. Epub 2018 Jun 25.
Gastric cancer (GC) is one of the most common malignant tumors with a high mortality rate. Reversing the multi‑drug resistance (MDR) of GC offers the potential for significant enhancement of the effect of chemotherapy and improvement of prognosis. Aberrant microRNA expression can attribute to the pathogenesis of GC. However, the effects of microRNA (miR)‑195‑5p on the MDR of GC cells remains to be fully elucidated. In the present study, the effect of miR‑195‑5p in regulating the MDR of GC cells was investigated. Reverse transcription quantitative‑polymerase chain reaction was used to analyze the levels of miR‑195‑5p in GC cells. Western blot analysis was performed to analyze the protein levels of ZNF139, P‑gp, BCL‑2 and MRP1. The chemosensitivity of GC cells was determined by MTT. The results showed that the expression of miR‑195‑5p was decreased in poorly differentiated GC tissues with a higher chemosensitivity. The overexpression of miR‑195‑5p promoted the chemosensitivity of GC cells. Bioinformatics analysis indicated that Zing finger 139 (ZNF139) was a target of miR‑195‑5p. miR‑195‑5p negatively regulated the expression of ZNF139 by binding to its 3'‑untranslated region. The silencing of ZNF139 promoted the chemosensitivity of GC cells, and the downregulation of ZNF139 reversed the effect of miR‑195‑5p inhibitor on the chemosensitivity of GC cells. In conclusion, miR‑195‑5p regulated the MDR of GC cells via targeting ZNF139.
胃癌（GC）是一种常见的恶性肿瘤，死亡率很高。逆转 GC 的多药耐药性（MDR）可能显著增强化疗效果并改善预后。异常的 microRNA 表达可能与 GC 的发病机制有关。然而，microRNA（miR）-195-5p 对 GC 细胞 MDR 的影响仍有待充分阐明。在本研究中，研究了 miR-195-5p 调节 GC 细胞 MDR 的作用。逆转录定量聚合酶链反应用于分析 GC 细胞中 miR-195-5p 的水平。Western blot 分析用于分析 ZNF139、P-糖蛋白、BCL-2 和 MRP1 的蛋白水平。MTT 用于测定 GC 细胞的化疗敏感性。结果表明，miR-195-5p 在化学敏感性较高的低分化 GC 组织中表达降低。miR-195-5p 的过表达促进了 GC 细胞的化疗敏感性。生物信息学分析表明，锌指蛋白 139（ZNF139）是 miR-195-5p 的靶标。miR-195-5p 通过结合其 3'非翻译区负调控 ZNF139 的表达。ZNF139 的沉默促进了 GC 细胞的化疗敏感性，而 ZNF139 的下调逆转了 miR-195-5p 抑制剂对 GC 细胞化疗敏感性的影响。综上所述，miR-195-5p 通过靶向 ZNF139 调节 GC 细胞的 MDR。
