microRNA-7 impairs autophagy-derived pools of glucose to suppress pancreatic cancer progression

Autor: Ling Tian, Chenyun Dai, Ming-jie Jiang, Chi Fang, Qian Huang, Zhu Mei, Dian-na Gu, Juan-juan Dai
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Time Factors
Autophagy-Related Proteins
AMP-Activated Protein Kinases
Autophagy-Related Protein 7
Metastasis
0302 clinical medicine
AMP-Activated Protein Kinase Kinases
Cell Movement
Transduction
Genetic
Glycolysis
Mice
Inbred BALB C
TOR Serine-Threonine Kinases
Tumor Burden
Cysteine Endopeptidases
Oncology
030220 oncology & carcinogenesis
Disease Progression
Signal Transduction
medicine.medical_specialty
Genetic Vectors
Mice
Nude
Protein Serine-Threonine Kinases
Biology
03 medical and health sciences
Cell Line
Tumor
Internal medicine
Pancreatic cancer
Autophagy
medicine
Animals
Humans
Neoplasm Invasiveness
PI3K/AKT/mTOR pathway
Cell Proliferation
Tumor microenvironment
Lentivirus
Genetic Therapy
ULK2
medicine.disease
Xenograft Model Antitumor Assays
Pancreatic Neoplasms
MicroRNAs
Glucose
030104 developmental biology
Endocrinology
Anaerobic glycolysis
Cancer research
Zdroj: Cancer Letters. 400:69-78
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2017.04.020
Popis: 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.
Databáze: OpenAIRE
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