Open AccessUpregulation of microRNA-200a associates with tumor proliferation, CSCs phenotype and chemosensitivity in ovarian cancer
Author(s) -
N Liu,
Lele Zhong,
Juan Zeng,
X Zhang,
Qingzhu Yang,
Daixiang Liao,
Y Wang,
G Chen
Publication year - 2015
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2015_066
Subject(s) - ovarian cancer , paclitaxel , cancer research , downregulation and upregulation , cisplatin , cell growth , microrna , biology , cancer , cell cycle , population , medicine , chemotherapy , biochemistry , genetics , gene , environmental health
Ovarian cancer is a lethal gynecologic malignancy and always has a poor prognosis. Despite new treatments modalities, the long term outcomes had not been significantly improved in the past 30 years. Although microRNA-200a (miR-200a) has been reported to be a prognostic marker in ovarian cancer, it's exact role in ovarian cancer remain unclear. In this study, we inserted the response element of miR-200a in ovarian cancer cell line via lentivirus-mediated transgene in vitro, and qRT-PCR (real time quantitative reverse transcription PCR) assay confirmed that miR-200a was up regulated compared with control. Then colony-formation assay, cell cycle analysis, CCK8 assays in vitro and xenograft experiments in vivo were performed and verified that miR-200a promoted proliferation, while blocked the formation of tumor spheroids and reduced the ratio of SP (side population) cells in ovarian cancer. Finally, we invalidated that miR-200a significantly enhanced the chemosensitivity of paclitaxel but not cisplatin in both adherent culture and sphere culture. Taken together, we demonstrated that upregulation miR-200a promoted proliferation and inhibited CSCs phenotype in OVCAR-3 ovarian cancer cell line, combined with cell cycle-targeting drug paclitaxel could effectively eliminate the "side effects" of proliferation, and showed evidences that this strategy may be promising for ovarian cancer treatment.