MicroRNA-224 aggrevates tumor growth and progression by targeting mTOR in gastric cancer.
Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumors, including gastric cancer. Aberrant miR-224 expression has been indicated in tumor growth, the mechanism of miR-224 promoting the proliferation and metastatic ability for gastric cancer remains unclear. Accumulating evidence reports that mTOR signal pathway plays an important role in the cellular process, such as apoptosis, cell growth and proliferation. The goal of the present study was to identify whether miR-224 could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting mTOR expression. Real-time PCR (RT-PCR) was used to quantify miR-224 expression in vitro and in vivo experiments. Luciferase reporter assays were performed to confirm the activity of mTOR pathway, and immunofluorescence staining assay was conducted to observe apoptosis and cell proliferation ability. Bioinformatics as well as cell luciferase function studies distinguished the direct modulation of miR-224 on the 3'-UTR of the mTOR, which leads to the inactivation of apoptosis signaling and the activation of cell proliferation. In addition, inhibition of miR-224 significantly reduced the expression of mTOR and improved caspase-9/3 expression while decreased cyclin D1/2 levels, attenuating gastric cancer cell proliferation. Therefore, the present study revealed the mechanistic links between miR-224 and mTOR in the pathogenesis of gastric cancer through modulation of caspase-9/3 and cyclin D1/2. In addition, targeting miR-224 could serve as a novel strategy for future gastric cancer therapy.
Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Ying
Y
Zhang
Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Chang-Feng
CF
Li
Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Lian-Jun
LJ
Ma
Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Meng
M
Ding
Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Bin
B
Zhang
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*
C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases