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Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun.
Cell Physiol Biochem. 2018; 51(1):129-141.CP

Abstract

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.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30439707

Citation

Jiang, Ying, et al. "Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance By Targeting C-Jun." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 51, no. 1, 2018, pp. 129-141.
Jiang Y, Jiang J, Jia H, et al. Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun. Cell Physiol Biochem. 2018;51(1):129-141.
Jiang, Y., Jiang, J., Jia, H., Qiao, Z., & Zhang, J. (2018). Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 51(1), 129-141. https://doi.org/10.1159/000495169
Jiang Y, et al. Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance By Targeting C-Jun. Cell Physiol Biochem. 2018;51(1):129-141. PubMed PMID: 30439707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by Targeting C-Jun. AU - Jiang,Ying, AU - Jiang,Jing, AU - Jia,Haiqing, AU - Qiao,Zhiwei, AU - Zhang,Jingru, Y1 - 2018/11/15/ PY - 2018/03/13/received PY - 2018/11/07/accepted PY - 2018/11/16/pubmed PY - 2018/12/12/medline PY - 2018/11/16/entrez KW - C-Jun KW - Cisplatin KW - Ovarian cancer KW - miR-139-5p SP - 129 EP - 141 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 51 IS - 1 N2 - 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. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/30439707/Recovery_of_miR_139_5p_in_Ovarian_Cancer_Reverses_Cisplatin_Resistance_by_Targeting_C_Jun_ L2 - https://www.karger.com?DOI=10.1159/000495169 DB - PRIME DP - Unbound Medicine ER -