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Reversal of cisplatin resistance by microRNA-139-5p-independent RNF2 downregulation and MAPK inhibition in ovarian cancer.
Am J Physiol Cell Physiol. 2018 08 01; 315(2):C225-C235.AJ

Abstract

Some microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression has been reported to correlate with chemoresistance of cancer cells. Therefore, the present study aims at investigating the effects of microRNA-139-5p (miR-139-5p) on cisplatin resistance of ovarian cancer (OC) with involvement of ring finger protein 2 (RNF2) and the mitogen-activated protein kinase (MAPK) signaling pathway. OC tissues were obtained from 66 primary OC patients. The cisplatin-sensitive A2780 and cisplatin-resistant A2780/DDP cell lines were collected for construction of RNF2 silencing and overexpressed plasmids. Cell vitality and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin V-FITC/propidium iodide double-staining, respectively. Next, expression of RNF2, extracellular signal-related kinase, and p38 was determined by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Finally, the volume of xenograft tumors in BALB/c nude mice was detected. RNF2 and miR-139-5p were identified to be involved in OC. In addition, MAPK activation and RNF2 were related to cisplatin resistance of OC. miR-139-5p was downregulated in cisplatin-resistant OC tissues, and miR-139-5p overexpression could inhibit cell vitality, reduce cisplatin resistance, and promote apoptosis of OC cells. Furthermore, miR-139-5p combined with MAPK inhibitors more obviously reduced cisplatin resistance of OC. Taken together, this study demonstrated that miR-139-5p overexpression combined with inactivation of the MAPK signaling pathway can reverse the cisplatin resistance of OC by suppressing RNF2. Thus, miR-139-5p overexpression might be a future therapeutic strategy for OC.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, People's Republic of China.Medical Insurance Management Office, Economic and Technological Development Zone, People's Hospital of Linyi, Linyi, People's Republic of China.Department of Obstetrics and Gynecology, Economic and Technological Development Zone, People's Hospital of Linyi, Linyi, People's Republic of China.Department of Obstetrics and Gynecology, Economic and Technological Development Zone, People's Hospital of Linyi, Linyi, People's Republic of China.Department of Obstetrics and Gynecology, Economic and Technological Development Zone, People's Hospital of Linyi, Linyi, People's Republic of China.Department of Reproductive Medicine, Linyi People's Hospital, Linyi, People's Republic of China.Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29719173

Citation

Chen, Ying, et al. "Reversal of Cisplatin Resistance By microRNA-139-5p-independent RNF2 Downregulation and MAPK Inhibition in Ovarian Cancer." American Journal of Physiology. Cell Physiology, vol. 315, no. 2, 2018, pp. C225-C235.
Chen Y, Cao XY, Li YN, et al. Reversal of cisplatin resistance by microRNA-139-5p-independent RNF2 downregulation and MAPK inhibition in ovarian cancer. Am J Physiol, Cell Physiol. 2018;315(2):C225-C235.
Chen, Y., Cao, X. Y., Li, Y. N., Qiu, Y. Y., Li, Y. N., Li, W., & Wang, H. (2018). Reversal of cisplatin resistance by microRNA-139-5p-independent RNF2 downregulation and MAPK inhibition in ovarian cancer. American Journal of Physiology. Cell Physiology, 315(2), C225-C235. https://doi.org/10.1152/ajpcell.00283.2017
Chen Y, et al. Reversal of Cisplatin Resistance By microRNA-139-5p-independent RNF2 Downregulation and MAPK Inhibition in Ovarian Cancer. Am J Physiol, Cell Physiol. 2018 08 1;315(2):C225-C235. PubMed PMID: 29719173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of cisplatin resistance by microRNA-139-5p-independent RNF2 downregulation and MAPK inhibition in ovarian cancer. AU - Chen,Ying, AU - Cao,Xiao-Yun, AU - Li,Ying-Ni, AU - Qiu,Yu-Yan, AU - Li,Ying-Na, AU - Li,Wen, AU - Wang,Hui, Y1 - 2018/05/02/ PY - 2018/5/3/pubmed PY - 2019/7/2/medline PY - 2018/5/3/entrez KW - MAPK signaling pathway KW - cisplatin resistance KW - microRNA-139-5p KW - ovarian cancer KW - ring finger protein 2 SP - C225 EP - C235 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 315 IS - 2 N2 - Some microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression has been reported to correlate with chemoresistance of cancer cells. Therefore, the present study aims at investigating the effects of microRNA-139-5p (miR-139-5p) on cisplatin resistance of ovarian cancer (OC) with involvement of ring finger protein 2 (RNF2) and the mitogen-activated protein kinase (MAPK) signaling pathway. OC tissues were obtained from 66 primary OC patients. The cisplatin-sensitive A2780 and cisplatin-resistant A2780/DDP cell lines were collected for construction of RNF2 silencing and overexpressed plasmids. Cell vitality and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin V-FITC/propidium iodide double-staining, respectively. Next, expression of RNF2, extracellular signal-related kinase, and p38 was determined by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Finally, the volume of xenograft tumors in BALB/c nude mice was detected. RNF2 and miR-139-5p were identified to be involved in OC. In addition, MAPK activation and RNF2 were related to cisplatin resistance of OC. miR-139-5p was downregulated in cisplatin-resistant OC tissues, and miR-139-5p overexpression could inhibit cell vitality, reduce cisplatin resistance, and promote apoptosis of OC cells. Furthermore, miR-139-5p combined with MAPK inhibitors more obviously reduced cisplatin resistance of OC. Taken together, this study demonstrated that miR-139-5p overexpression combined with inactivation of the MAPK signaling pathway can reverse the cisplatin resistance of OC by suppressing RNF2. Thus, miR-139-5p overexpression might be a future therapeutic strategy for OC. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/29719173/Reversal_of_cisplatin_resistance_by_microRNA_139_5p_independent_RNF2_downregulation_and_MAPK_inhibition_in_ovarian_cancer_ L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00283.2017?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -