Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 38, Issue 6, Pages 2366-2374Publisher
Cell Physiol Biochem Press GmbH & Co
DOI: 10.1159/000445589
Keywords
MiR-221; Pancreatic ductal adenocarcinoma; Capan-2; PTEN; Akt
Categories
Funding
- National Natural Science Foundation of China [81170406, 81070343, 81370559, 81400635]
- Shanghai Municipal Commission of Health and Family Planning [2014ZYJB0201, SHDC12014122]
- Shanghai Science and Technology Committee [14411971500]
- Chinese Foundation for Hepatitis Prevention and Control [TQGB20140141]
- Shanghai Innovation Program [12431901002]
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Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as critical regulators of cancer cell proliferation. The effect of miR-221 on cancer cell growth could be significantly changeable in different cell lines. Although miR-221 was reported to promote the cell growth of pancreatic ductal adenocarcinoma (PDAC) cells, its role in Capan-2 cell line is largely unknown. Methods: Capan-2 cells were transfected with miR-221 mimics, inhibitors, or negative controls. Cell Counting Kit-8 was used to determine cell viability. EdU staining and cell cycle analysis were used to measure cell proliferation. Western blotting was used to detect the expression levels of PTEN and phospho-Akt. The PI3K-Akt pathway activator SC-79 and inhibitor LY294002 were used to perform the rescue experiment in determining cell proliferation. Results: Overexpressing miR-221 significantly increased cell vitality and promoted cell proliferation and G1-to-S phase transition of the cell cycle in Capan-2 cells, while inhibition of miR-221 decreased that. The protein level of PTEN in Capan-2 cells was downregulated by overexpressing miR-221, while upregulated by inhibiting miR-221. Consistently, enhanced phosphorylation of Akt(Ser473) was observed in miR-221 overexpressed Capan-2 cells, and the opposite result was found in miR-221 inhibited cells. LY294002 restored the pro-proliferation effect of miR-221 on Capan-2 cells, while SC-79 had no additional effect on cell proliferation in Capan-2 cells transfected with miR-221 mimics. Conclusion: Our study indicates that miR-221 is an oncogenic mi RNA which promotes Capan-2 cells proliferation by targeting PTEN-Akt pathway. (C) 2016 The Author(s) Published by S. Karger AG, Basel
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