Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, Anhui, P.R. China.
Department of Oncology, Anhui Cancer Hospital, Hefei, Anhui, P.R. China.
Oncol Res. 2018 Jul 5;26(6):901-911. doi: 10.3727/096504017X15061902533715. Epub 2017 Sep 26.
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.
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。