LncRNA-H19 regulates chemoresistance to carboplatin in epithelial ovarian cancer through microRNA-29b-3p and STAT3

Tian, Xueye; Zuo, Xiaohang; Hou, Meng; Li, Chen; Teng, Yue

doi:10.7150/jca.58979

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J Cancer 2021; 12(19):5712-5722. doi:10.7150/jca.58979 This issue Cite

Research Paper

LncRNA-H19 regulates chemoresistance to carboplatin in epithelial ovarian cancer through microRNA-29b-3p and STAT3

Xueye Tian^1*, Xiaohang Zuo^2*, Meng Hou¹, Chen Li¹, Yue Teng^1✉

1. Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
2. Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
* These authors have contributed equally to this work.

Citation:

Tian X, Zuo X, Hou M, Li C, Teng Y. LncRNA-H19 regulates chemoresistance to carboplatin in epithelial ovarian cancer through microRNA-29b-3p and STAT3. J Cancer 2021; 12(19):5712-5722. doi:10.7150/jca.58979. https://www.jcancer.org/v12p5712.htm

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Abstract

Background: Platinum-based chemotherapy is part of current standard treatment for epithelial ovarian cancer (EOC). However, chemoresistance often rapidly developed, leading to chemotherapy failure and unfavored prognosis. Increasing evidence has demonstrated the important role of oncogenic long noncoding RNA H19 in various cancers, including EOC. No current study is available in exploring the role of lncRNA-H19 in carboplatin resistance of EOC and its underlying mechanism.

Methods: Levels of lncRNA-H19, miR-29b-3p, and STAT3 mRNA were measured by qRT-PCR. The 50% inhibitory concentration value was detected with Cell Counting Kit-8 (CCK8). Colony-formation and CCK8 assays were employed to measure cell viability. Cell migration and invasion ability was evaluated with transwells. Western blot assay was utilized to measure P-gp, MRP1, LRP, and STAT3 protein levels. The targeting between lncRNA-H19 and miR-29b-3p, as well as miR-29b-3p and STAT3, was verified by dual-luciferase, RNA immunoprecipitation, and RNA pull-down experiments.

Results: lncRNA-H19 and STAT3 were sharply increased, while miR-29b-3p was decreased in carboplatin-resistant EOC. Carboplatin efficacy was enhanced by lncRNA-H19 silencing in chemo-resistant EOC cells. lncRNA-H19 served as a competing endogenous RNA of miR-29b-3p, causing the derepression of miR-29b-3p downstream target STAT3, leading to chemoresistance in carboplatin-tolerated EOC.

Conclusions: The lncRNA-H19/miR-29b-3p axis improved carboplatin resistance of EOC by targeting STAT3, indicating a possible approach to improving chemotherapy for EOC.

Keywords: lncRNA-H19, miR-29b-3p, STAT3, carboplatin resistance, epithelial ovarian cancer

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APA

Tian, X., Zuo, X., Hou, M., Li, C., Teng, Y. (2021). LncRNA-H19 regulates chemoresistance to carboplatin in epithelial ovarian cancer through microRNA-29b-3p and STAT3. Journal of Cancer, 12(19), 5712-5722. https://doi.org/10.7150/jca.58979.

ACS

Tian, X.; Zuo, X.; Hou, M.; Li, C.; Teng, Y. LncRNA-H19 regulates chemoresistance to carboplatin in epithelial ovarian cancer through microRNA-29b-3p and STAT3. J. Cancer 2021, 12 (19), 5712-5722. DOI: 10.7150/jca.58979.

NLM

CSE

Tian X, Zuo X, Hou M, Li C, Teng Y. 2021. LncRNA-H19 regulates chemoresistance to carboplatin in epithelial ovarian cancer through microRNA-29b-3p and STAT3. J Cancer. 12(19):5712-5722.

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