Open AccessRecovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun
Author(s) -
Ying Jiang,
Jing Jiang,
Haiqing Jia,
Zhiwei Qiao,
Jingru Zhang
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000495169
Subject(s) - cisplatin , apoptosis , ovarian cancer , viability assay , cancer research , flow cytometry , microrna , microbiology and biotechnology , chemistry , mtt assay , blot , western blot , cell culture , biology , cancer , chemotherapy , biochemistry , gene , genetics
Background/Aims: In platinum-based chemotherapy for ovarian cancer, acquired drug resistance is a frequent occurrence. Because recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is partly responsible for the induction of acquired drug resistance in cancers, we hypothesized that correcting the dysregulation of key miRNAs would reverse the acquired resistance to platinum-based drugs in ovarian cancer. Methods: Cisplatin-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3-R and A2780-R, respectively) were established by long-term exposure to cisplatin. MTT assays were performed to evaluate the viability of SKOV3, SKOV3-R, A2780, and A2780-R cells. Quantitative PCR was used to examine the expression of miR-139-5p in these cell lines. The regulatory mechanism was confirmed by western blot analysis and luciferase reporter assays. After treatment with miR-139-5p and cisplatin, mitochondrial membrane potential and apoptosis were measured by using flow cytometry. Interaction with c-Jun and activating transcription factor 2 (ATF2) was evaluated by co-immunoprecipitation. Expression of B-cell lymphoma-extra large (Bcl-xl) and activation of caspase-9 and caspase-3 were detected by western blotting. Results: Expression of miR-139-5p was decreased in SKOV3-R and A2780-R cells. Recovery of miR-139-5p increased the sensitivity of SKOV3-R and A2780-R cells to cisplatin treatment, inhibited the interaction of c-Jun and ATF2, and decreased Bcl-xl expression in SKOV3-R and A2780-R cells. Expression of miR-139-5p promoted cisplatin-induced mitochondrial apoptosis through binding the 3′ untranslated region of c-Jun mRNA. Conclusion: Recovery of miR-139-5p suppressed the expression of c-Jun and thus reversed cisplatin-resistance in ovarian cancer.