Department of Surgery, Shigatse People's Hospital, Shigatse 857000, P.R. China.
Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Mol Cells. 2018 Jun;41(6):532-544. doi: 10.14348/molcells.2018.2211. Epub 2018 Jun 14.
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR-374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.
胃肠道间质瘤(GIST)是胃肠道(GI)最常见的间叶性肿瘤。为了探索 GIST 的新治疗方法,我们假设 miR-374b 靶向 PTEN 基因介导的 PI3K/Akt 信号转导通路对人胃肠道间质瘤(GIST)细胞增殖和凋亡的影响。我们从 143 例 GIST 患者中获得 GIST 组织和相邻正常组织,以测量 miR-374b、PTEN、PI3K、Akt、caspase9、Bax、MMP2、MMP9、ki67、PCNA、P53 和 cyclinD1 的水平。最后,检测细胞活力、细胞周期和细胞凋亡。根据 DEGs 的 KFGG 分析,PTEN 参与多种信号通路,miRs 与癌症的发生发展有关。结果表明,miR-374b 在 GIST 组织中高表达,而 PTEN 下调。miR-374b、PI3K、AKT 和 PTEN 的水平与肿瘤直径和病理分期有关。此外,miR-374b 增加了 GIST-T1 细胞中 PI3K、Akt、MMP2、MMP9、P53 和 cyclinD1 的 mRNA 和蛋白水平,表明 miR-374b 在 GIST-T1 细胞中激活了 PI3K/Akt 信号通路。此外,miR-374b 促进了 GIST 细胞的活力、迁移、侵袭和细胞周期进入,并抑制了细胞凋亡。总之,结果表明,miR-374b 通过 PI3K/Akt 信号通路靶向 PTEN 基因促进了人 GIST 细胞的活力并抑制了其凋亡。因此,本研究为 GIST 的治疗提供了一个新的潜在靶点。