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IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells.
Oncotarget. 2017 Jun 13; 8(24):39154-39166.O

Abstract

Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target. Importantly, the resulting IL-6R/STAT3/miR-204 feedback loop was identified in patients with EOC, and its activity correlated with chemosensitivity. Moreover, exogenous miR-204 blocked this circuit and enhanced cDDP sensitivity both in vitro and in vivo by inactivating IL-6R/STAT3 signaling and subsequently decreasing the expression of anti-apoptotic proteins. Our findings illustrate the function of this feedback loop in cDDP-based therapy and may offer a broadly useful approach to improve EOC therapy.

Authors+Show Affiliations

Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China. Jiangsu University, Medical School, Zhenjiang, Jiangsu 212003, China.Jiangsu University, Medical School, Zhenjiang, Jiangsu 212003, China. Department of Oncology, The Affiliated People Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Oncology, The Affiliated People Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Jiangsu University, Medical School, Zhenjiang, Jiangsu 212003, China.Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28388577

Citation

Zhu, Xiaolan, et al. "IL-6R/STAT3/miR-204 Feedback Loop Contributes to Cisplatin Resistance of Epithelial Ovarian Cancer Cells." Oncotarget, vol. 8, no. 24, 2017, pp. 39154-39166.
Zhu X, Shen H, Yin X, et al. IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells. Oncotarget. 2017;8(24):39154-39166.
Zhu, X., Shen, H., Yin, X., Long, L., Chen, X., Feng, F., Liu, Y., Zhao, P., Xu, Y., Li, M., Xu, W., & Li, Y. (2017). IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells. Oncotarget, 8(24), 39154-39166. https://doi.org/10.18632/oncotarget.16610
Zhu X, et al. IL-6R/STAT3/miR-204 Feedback Loop Contributes to Cisplatin Resistance of Epithelial Ovarian Cancer Cells. Oncotarget. 2017 Jun 13;8(24):39154-39166. PubMed PMID: 28388577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells. AU - Zhu,Xiaolan, AU - Shen,Huiling, AU - Yin,Xinming, AU - Long,Lulu, AU - Chen,Xiaofang, AU - Feng,Fan, AU - Liu,Yueqin, AU - Zhao,Peiqing, AU - Xu,Yue, AU - Li,Mei, AU - Xu,Wenlin, AU - Li,Yuefeng, PY - 2017/01/23/received PY - 2017/03/02/accepted PY - 2017/4/8/pubmed PY - 2018/6/8/medline PY - 2017/4/8/entrez KW - EOC KW - IL-6R KW - STAT3 KW - chemoresistance KW - miR-204 SP - 39154 EP - 39166 JF - Oncotarget JO - Oncotarget VL - 8 IS - 24 N2 - Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target. Importantly, the resulting IL-6R/STAT3/miR-204 feedback loop was identified in patients with EOC, and its activity correlated with chemosensitivity. Moreover, exogenous miR-204 blocked this circuit and enhanced cDDP sensitivity both in vitro and in vivo by inactivating IL-6R/STAT3 signaling and subsequently decreasing the expression of anti-apoptotic proteins. Our findings illustrate the function of this feedback loop in cDDP-based therapy and may offer a broadly useful approach to improve EOC therapy. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28388577/IL_6R/STAT3/miR_204_feedback_loop_contributes_to_cisplatin_resistance_of_epithelial_ovarian_cancer_cells_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=16610 DB - PRIME DP - Unbound Medicine ER -