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Article

Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6

  • Authors:
    • Xiaofang Xu
    • Shengfang Ge
    • Renbing Jia
    • Yixiong Zhou
    • Xin Song
    • He Zhang
    • Xianqun Fan
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
  • Pages: 2789-2796
    |
    Published online on: April 7, 2015
       https://doi.org/10.3892/or.2015.3900
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Abstract

Previous findings showed that miR-181b is upregulated under hypoxic conditions in retinoblastoma cells. Since hypoxia is a common feature of retinoblastoma that affects tumor progression as well as tumor therapy, in the present study, we investigated the regulatory mechanism of miR-181b under hypoxic conditions, and examined the role of miR-181b in retinoblastoma responses to hypoxia (chemoresistance and angiogenesis) and possible downstream genes. The level of hypoxia-inducible factor-1α (HIF-1α) and miR-181b was detected to examine the link between them. Tube formation and cell cytotoxicity assays were used to clarify the effects of miR-181b on hypoxic responses of retinoblastoma cells. Bioinformatics analysis was performed to predict potential targets of miR-181b and western blotting was used to verify these targets. The results showed a significantly increased expression of HIF-1α in hypoxia-treated retinoblastoma cells. Downregulation of HIF-1α using a small‑interfering RNA (siRNA) knockdown technology did not decrease the expression of miR-181b. Through gain- and loss-of-function studies, miR-181b was demonstrated to significantly stimulate the ability of capillary tube formation of endothelial cells. Programmed cell death-10 (PDCD10) and GATA binding protein 6 (GATA6) were identified as the target genes of miR‑181b. To the best of our knowledge, results of the present study provide the first evidence that miR-181b was upregulated by hypoxia in retinoblastoma in an HIF-1α-independent manner. miR-181b increased tumor angiogenesis of retinoblastoma cells. Additionally, miR-181b exerts its angiogenic function, at least in part, by inhibiting PDCD10 and GATA6. Thus, it is a new potentially useful therapeutic target for retinoblastoma.
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Copy and paste a formatted citation
Spandidos Publications style
Xu X, Ge S, Jia R, Zhou Y, Song X, Zhang H and Fan X: Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6. Oncol Rep 33: 2789-2796, 2015.
APA
Xu, X., Ge, S., Jia, R., Zhou, Y., Song, X., Zhang, H., & Fan, X. (2015). Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6. Oncology Reports, 33, 2789-2796. https://doi.org/10.3892/or.2015.3900
MLA
Xu, X., Ge, S., Jia, R., Zhou, Y., Song, X., Zhang, H., Fan, X."Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6". Oncology Reports 33.6 (2015): 2789-2796.
Chicago
Xu, X., Ge, S., Jia, R., Zhou, Y., Song, X., Zhang, H., Fan, X."Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6". Oncology Reports 33, no. 6 (2015): 2789-2796. https://doi.org/10.3892/or.2015.3900
Copy and paste a formatted citation
x
Spandidos Publications style
Xu X, Ge S, Jia R, Zhou Y, Song X, Zhang H and Fan X: Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6. Oncol Rep 33: 2789-2796, 2015.
APA
Xu, X., Ge, S., Jia, R., Zhou, Y., Song, X., Zhang, H., & Fan, X. (2015). Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6. Oncology Reports, 33, 2789-2796. https://doi.org/10.3892/or.2015.3900
MLA
Xu, X., Ge, S., Jia, R., Zhou, Y., Song, X., Zhang, H., Fan, X."Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6". Oncology Reports 33.6 (2015): 2789-2796.
Chicago
Xu, X., Ge, S., Jia, R., Zhou, Y., Song, X., Zhang, H., Fan, X."Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6". Oncology Reports 33, no. 6 (2015): 2789-2796. https://doi.org/10.3892/or.2015.3900
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