کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525508 1546669 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticlemicroRNA-7 impairs autophagy-derived pools of glucose to suppress pancreatic cancer progression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticlemicroRNA-7 impairs autophagy-derived pools of glucose to suppress pancreatic cancer progression
چکیده انگلیسی


- PDAC utilizes autophagy as a survival strategy to provide glucose to glycolysis.
- miR-7 inhibits autophagy to reduce the intracellular glucose supply to glycolysis.
- miR-7 represses autophagy via directly target LKB1, ULK2, ATG4A and ATG7.
- miR-7 inhibits PDAC proliferation and metastasis in vitro and in vivo.
- Lentivirus-mediated miR-7 reduces tumor growth in PDAC PDX model.

Pancreatic cancer commonly addicts to aerobic glycolysis, and abnormally activates autophagy to adapt the stringent metabolic microenvironment. microRNA-7 (miR-7) was supposed to modulate various gastrointestinal cancer progression. We wonder whether miR-7 could destroy the reprogrammed metabolic homeostasis in pancreatic cancer via modulating the level of autophagy, and further affect tumor proliferation and survival. Herein, we first reported that pancreatic cancer could take advantage of autophagy as a survival strategy to provide essential glucose required for glycolysis metabolism. Of note, under the stressful tumor microenvironment, miR-7 could repress autophagy through up-regulation of LKB1-AMPK-mTOR signaling, and directly targeting the stages of autophagy induction and vesicle elongation to reduce the supply of intracellular glucose to glycolysis metabolism. Furthermore, miR-7 inhibited pancreatic cancer cell proliferation and metastasis in vitro and in vivo. Consistently, lentivirus-mediated miR-7 effectively reduced the growth of patient-derived xenograft by interfering glycolysis via inhibition of autophagy. Together, these data suggested miR-7 might function as an important regulator to impair autophagy-derived pools of glucose to suppress pancreatic cancer progress. Hence, miR-7 might be a potential therapeutic target in pancreatic cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 400, 1 August 2017, Pages 69-78
نویسندگان
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