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MicroRNA-155 promotes apoptosis in SKOV3, A2780, and primary cultured ovarian cancer cells

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Tumor Biology

Abstract

MicroRNAs (miRNAs) are a large group of small non-coding RNAs that can negatively regulate gene expression at the post-transcriptional level. The deregulation of miRNAs has been associated with tumorigenesis, drug resistance, and prognosis in cancers. Deregulated miR-155 has been reported in numerous cancers; however, its function remains unclear. 4′,6-Diamidino-2-phenylindole (DAPI) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) techniques were used to determine the effects of a miR-155 mimic or inhibitor on the apoptotic ratio of ovarian cancer cells induced by cisplatin. Bioinformatic predictions, the dual-luciferase reporter assay, and western blot analysis were used to detect how miR-155 regulates X-linked inhibitor of apoptosis protein (XIAP). We demonstrated that a miR-155 mimic could decrease the IC50 value of cisplatin in SKOV3 ovarian cancer cells. Subsequently, gain- and loss-of-function analyses with a miR-155 mimic and inhibitor showed that miR-155 sensitizes ovarian cancer cells to cisplatin. Furthermore, the results from the luciferase assays and western blot analysis identified XIAP as the direct target of miR-155. In addition, introducing XIAP cDNA without a three prime untranslated region (3′-UTR) rescued the miR-155 promotion of apoptosis. These results indicate that miR-155 mediates cisplatin-induced apoptosis by targeting XIAP in ovarian cancer cells and that miR-155 could be a potential therapeutic target to increase the efficiency of ovarian cancer interventions.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (grant nos. 81101960 and 81572567), the Natural Science Foundation of Guangdong Province (grant no. S2013010012170), the Shenzhen Municipal Government of China (grant no. LXRY20121106142947958), and the Laboratory Opening Fund of Sun Yat-sen University (grant no. KF201329).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510260, China

    Wei Chen & Yuanli He

  2. Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Road, Guangzhou, 510260, China

    Wei Chen, Liuxuan Huang & Longshu Zhou

  3. Department of Obstetrics and Gynecology, Panyu Maternal and Child Care Service Centre of Guangzhou, Guangzhou, China

    Chenjun Hao

  4. State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, 132 East Waihuan Rd, Rm 312, Higher Education Mega, Guangzhou, 510006, China

    Wenshu Zeng, Xiaodi Li & Songshan Jiang

  5. Gene Science & Health Company, 3003 Shennan Road, Rm 2108, Shenzhen, 518000, China

    Xu Luo

  6. Department of Medical Genetics, Zhongshan Medical College, Sun Yat-sen University, Zhongshan Road 2, Guangzhou, 510080, China

    Zheng Chen

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  1. Wei Chen
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  2. Liuxuan Huang
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  9. Zheng Chen
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  10. Yuanli He
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Chen, W., Huang, L., Hao, C. et al. MicroRNA-155 promotes apoptosis in SKOV3, A2780, and primary cultured ovarian cancer cells. Tumor Biol. 37, 9289–9299 (2016). https://doi.org/10.1007/s13277-016-4804-9

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