MiR-34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin-based chemotherapy.

Abstract:

:Cisplatin (DDP)-based chemotherapy is a standard strategy for ovarian cancer (OC), while chemoresistance remains a major therapeutic challenge. Transcription factor SOX9 has been reported to be associated with tumor cell proliferation, metastasis, and chemoresistance. In the current study, we observed a higher SOX9 expression in OC cell lines; SOX9 overexpression might aggravate the chemoresistance of the OC cell to DDP, whereas its knockdown enhanced the chemoresistance. We screened for candidate microRNAs (miRNAs) which might target SOX9 using online tools and further verified the effect of miR-34c, one of the candidate miRNA that significantly inhibited SOX9 expression, in the regulation of OC cell proliferation and chemoresistance to DDP. Further, we verified the interaction between SOX9 and miR-34c, as well as the involvement of β-catenin signaling in this process. Through the analysis of the correlation between miR-34c expression and the clinical features of patients with OC, we revealed that miR-34c might inhibit OC cell proliferation and chemoresistance to improve the prognosis of patients with OC. Further, the expression of SOX9, β-catenin, and c-Myc in OC tissues was upregulated and inversely correlated with miR-34c expression, indicating that rescuing miR-34c expression, thus to inhibit SOX9, β-catenin, and c-Myc expression presents a promising strategy of reducing the chemoresistance of the OC cell to DDP.

journal_name

J Cell Biochem

authors

Xiao S,Li Y,Pan Q,Ye M,He S,Tian Q,Xue M

doi

10.1002/jcb.26865

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

2940-2953

issue

3

eissn

0730-2312

issn

1097-4644

journal_volume

120

pub_type

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