MiR-۵۷۰ inhibits cell proliferation and glucose metabolism by targeting IRS۱ and IRS۲ in human chronic myelogenous leukemia

Hong Zhao; Fei Liu; Ruichun Jia; Huiying Chang; Haixia Li; Meijuan Miao; Hui Wang; Zhiping Yang

MiR-۵۷۰ inhibits cell proliferation and glucose metabolism by targeting IRS۱ and IRS۲ in human chronic myelogenous leukemia

محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 20، شماره: 5

سال انتشار: 1396

نوع سند: مقاله ژورنالی

زبان: انگلیسی

مشاهده: 147

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لینک ثابت به این مقاله:

https://civilica.com/doc/1295723

شناسه ملی سند علمی:

JR_IJBMS-20-5_005

تاریخ نمایه سازی: 28 مهر 1400

چکیده مقاله:

Objective(s): Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disorder characterized by the accumulation of myeloid cells with a chromosomal translocation known as the Philadelphia chromosome. In this study, we investigated the roles of miR-۵۷۰ in CML development. Materials and Methods: Expression of miR-۵۷۰ in CML samples and cell lines was determined by qRT-PCR. Glucose uptake and ATP concentration detection assays were used to analyze cell glucose metabolism. MTT and western blot assays were performed for cell proliferation and apoptosis, respectively. The targets of miR-۵۷۰ were predicted by bioinformatics and confirmed using luciferase activity, qRT-PCR and western blot assays. Results: The expression levels of miR-۵۷۰ were significantly reduced in CML clinical samples and cells. Overexpression of miR-۵۷۰ inhibited cell proliferation, promoted apoptosis, and suppressed glucose metabolism in CML cells. Insulin receptor substrates (IRS) ۱ and IRS۲ were identified as direct targets of miR-۵۷۰. IRS۱ or IRS۲ were knocked down in K۵۶۲ cells.Loss of IRS۱/۲ expression led to suppressed cell proliferation, elevated apoptosis, and decreased glucose metabolism in CML cells, which is consistent with their roles as miR-۵۷۰ targets. Conclusion: MiR-۵۷۰ directly targeted IRS۱ and IRS۲ in CML, suppressing cell proliferation and glucose metabolism. MiR-۵۷۰ may provide a strategy for CML therapy.

کلیدواژه ها:

Chronic myelogenous leukemia ، IRS۱ ، IRS۲ ، miR-۵۷۰

نویسندگان

Hong Zhao