Antagonism of microRNA-99a promotes cell invasion and down-regulates E-cadherin expression in pancreatic cancer cells by regulating mammalian target of rapamycin.
MicroRNA-99a (miRNA-99a), a potential tumor suppressor, has been implicated in tumorigenesis of many human malignancies. However, the role of miRNA-99a in pancreatic cancer remains unclear. In the present study, we transfected miRNA-99a antagonism into human pancreatic cancer AsPC-1 cells to inhibit miRNA-99a expression and investigated its influence on cell migration and invasion as well as the underlying possible mechanisms. We found that miRNA-99a antagonism significantly increased proliferation, migration and invasion abilities of AsPC-1 cells, which was accompanied by increased expression of mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and α-SMA), and decreased expression of epithelial phenotype cell biomarker (E-cadherin). Interestingly, small interfering RNA (siRNA)-mediated knockdown of mammalian target of rapamycin (mTOR) remarkably restored miRNA-99a antagonism-induced down-regulation of E-cadherin. In conclusion, our data suggest that miRNA-99a is involved in pancreatic cancer migration and invasion by regulating mTOR, and may provide a target for effective therapies against pancreatic cancer.
Department of Pathology, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
Dan
D
Li
Department of Pathology, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
Xiaohan
X
Li
Department of Pathology, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
Wei
W
Cao
Department of Pathology, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
Yafei
Y
Qi
Department of Pathology, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. Electronic address: xianghong_yang@163.com.
Xianghong
X
Yang
D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D015820:Cadherins; C561679:MIRN99 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
E-cadherin; Invasion; Mammalian target of rapamycin; MicroRNA-99a; Migration; Pancreatic cancer