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http://dx.doi.org/10.14348/molcells.2018.2211

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway  

Long, Zi-Wen (Department of Surgery, Shigatse People's Hospital)
Wu, Jiang-Hong (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center)
Hong, Cai (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center)
Wang, Ya-Nong (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center)
Zhou, Ye (Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center)
Publication Information
Molecules and Cells / v.41, no.6, 2018 , pp. 532-544 More about this Journal
Abstract
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, MiR374b 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.
Keywords
apoptosis; gastrointestinal stromal tumor; microRNA-374b; PI3K/Akt signaling pathway; proliferation; PTEN;
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