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Cellular Oncology

, Volume 39, Issue 5, pp 463–471 | Cite as

Hypoxia-inducible microRNA-488 regulates apoptosis by targeting Bim in osteosarcoma

  • Chusong Zhou
  • Wei Tan
  • Hai Lv
  • Fei Gao
  • Jin SunEmail author
Original Paper

Abstract

Background

Osteosarcoma is a malignant bone cancer of which the survival rate is still low. One reason for this low survival rate is drug resistance. In the past, it has been shown that microRNAs may play critical roles in osteosarcoma development and drug resistance. The mechanisms by which osteosarcoma cells acquire this resistance have, however, remained largely unknown. Here, we aimed at assessing the role of microRNA-488 in the acquisition of drug resistance by osteosarcoma cells.

Methods

Quantitative RT-PCR was used to measure the expression of microRNA-488 in primary osteosarcoma samples and in osteosarcoma-derived cells, whereas microRNA-488 mimics and inhibitors were used to modify its expression in these cells. Luciferase reporter, Western blotting, cell viability, apoptosis and ChIP assays were used to assess the various effects of modified microRNA-488 expression in osteosarcoma-derived cells.

Results

We found that microRNA-488 is over-expressed in primary osteosarcoma tissues and osteosarcoma-derived cells and that hypoxia can induce microRNA-488 expression via binding to the hypoxia response element (HRE) in its promoter. We also found that exogenous over-expression of microRNA-488 promotes the proliferation, reduces the apoptosis and decreases the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the tumor suppressor Bim, which is a mediator of apoptosis. In contrast, we found that transfection of a microRNA-488 inhibitor resulted in an increase in both apoptosis and drug sensitivity, and a decrease in proliferation.

Conclusions

Our data suggest that miRNA-488 may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas.

Keywords

microRNA-488 Bim Drug resistance Apoptosis Osteosarcoma 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Funding

This study was supported by grants from the National Science Foundation of China (81,372,869).

Ethical standard

This article does not contain any studies with animals performed by any of the authors. All patients provided informed consent prior to inclusion in this study.

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Copyright information

© International Society for Cellular Oncology 2016

Authors and Affiliations

  • Chusong Zhou
    • 1
  • Wei Tan
    • 2
  • Hai Lv
    • 1
  • Fei Gao
    • 3
  • Jin Sun
    • 2
    Email author
  1. 1.Department of Bone, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Department of BoneThe Third People HospitalHuizhouChina
  3. 3.Department of BoneDonghua HospitalDongguanChina

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