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Authors Feng X, Liu N, Deng S, Zhang DD, Wang KX, Lu MS
Received 8 July 2017
Accepted for publication 14 September 2017
Published 12 December 2017 Volume 2017:10 Pages 5899—5906
DOI https://doi.org/10.2147/OTT.S145833
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Samir Farghaly
Abstract: Resistance
to chemotherapy is a primary problem for the effective treatment of ovarian
cancer. Recently, increasing evidence has demonstrated that miRNAs modulate
many important molecular pathways involved in chemotherapy. Previous studies
demonstrated that miR-199a affected ovarian cancer cell resistance to cisplatin
(DDP). However, the role of miR-199a and its target genes in determination of
ovarian cancer sensitivity to DDP remains unclear. Quantitative reverse transcription
polymerase chain reaction was used to detect the expression levels of miR-199a
in ovarian cancer tissues and C13* and OV2008 cell lines. After transfection of
miR-199a mimic or inhibitor, flow cytometry was used to detect cell apoptosis
exposed to DDP. Enzyme-linked immunosorbent assay and Western blot assay were
applied to detect tumor necrosis factor-α levels and protein expression levels
of Bax, Fas, Fas-associated death domain, and caspase-8. The results indicated
that the expression of miR-199a was downregulated and hypoxia-inducible factor
1α (Hif1α) upregulated in the ovarian tumors compared with those in the
corresponding normal tissues. Besides, the expression levels of miR-199a were
significantly higher in OV2008 cells compared with those in C13* cells.
Moreover, suppression of Hif1α reversed the inhibiting function of miR-199a
inhibitor on DDP-induced apoptosis in the OV2008 cells. However, overexpression
of both miR-199a and Hif1α reduced DDP-induced apoptosis in C13* cells. In
conclusion, miR-199a may change DDP resistance in ovarian cancer by regulating
Hif1α.
Keywords: miR-199a, ovarian cancer, cisplatin resistance, Hif1α