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下调 microRNA-147 通过直接靶向 PTEN 抑制胃癌细胞增殖并增加其对 5-氟尿嘧啶的化疗敏感性。

Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN.

机构信息

Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, Anhui, P.R. China.

Department of Oncology, Anhui Cancer Hospital, Hefei, Anhui, P.R. China.

出版信息

Oncol Res. 2018 Jul 5;26(6):901-911. doi: 10.3727/096504017X15061902533715. Epub 2017 Sep 26.

Abstract

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. This study aimed to investigate the expression patterns, biological roles, and underlying mechanisms of microRNA-147 (miR-147) in gastric cancer. The present study demonstrated that miR-147 was significantly upregulated in gastric cancer tissues and cell lines. Downregulation of miR-147 decreased cell proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-fluorouracil (5-FU) through the cell apoptosis pathway. In addition, phosphatase and tensin homolog (PTEN) was mechanically identified as the direct target of miR-147 in gastric cancer. PTEN knockdown reversed the effects of miR-147 downregulation on the proliferation, chemosensitivity, and 5-FU-induced apoptosis of gastric cancer cells. Moreover, miR-147 regulated the PI3K/AKT signaling pathway in gastric cancer by targeting PTEN. In conclusion, miR-147 suppressed the proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-FU by promoting cell apoptosis through directly targeting PTEN and regulating the PI3K/AKT signaling pathway. This study provides important insight into the molecular mechanism that underlies the chemoresistance of gastric cancer cells. The results of this study could aid the development of a novel therapeutic strategy for gastric cancer.

摘要

胃癌是第四大常见恶性肿瘤,也是全球癌症相关死亡的第三大主要原因。本研究旨在探讨 microRNA-147(miR-147)在胃癌中的表达模式、生物学作用和潜在机制。本研究表明,miR-147 在胃癌组织和细胞系中显著上调。下调 miR-147 通过细胞凋亡途径降低胃癌细胞的增殖,并增强胃癌细胞对 5-氟尿嘧啶(5-FU)的化疗敏感性。此外,磷酸酶和张力蛋白同源物(PTEN)被机械鉴定为胃癌中 miR-147 的直接靶标。PTEN 敲低逆转了 miR-147 下调对胃癌细胞增殖、化疗敏感性和 5-FU 诱导凋亡的影响。此外,miR-147 通过靶向 PTEN 调节胃癌中的 PI3K/AKT 信号通路。总之,miR-147 通过直接靶向 PTEN 并调节 PI3K/AKT 信号通路促进细胞凋亡,抑制胃癌细胞的增殖并增强其对 5-FU 的化疗敏感性。本研究为胃癌细胞化疗耐药的分子机制提供了重要的见解。本研究的结果可能有助于开发治疗胃癌的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55ea/7844761/400a7df8e356/OR-26-901-g001.jpg

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