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TGF-β1-induced miR-202 mediates drug resistance by inhibiting apoptosis in human osteosarcoma

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

A number of studies have demonstrated that microRNAs play a critical role in osteosarcoma progression, therapy and drug resistance. MicroRNA-202 has proven to be dysregulated in many human cancer studies. This study aimed to explore miR-202 contributions to drug resistance in osteosarcoma.

Methods

miR-202 expression was measured by real-time PCR in patient tissues, cell lines or cells treated with TGF-β1, using siRNA to knock down the expression of Smad2, Smad3 and Smad4. miR-202 mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on cell apoptosis and drug resistance. Moreover, relationships of miR-202 level with PDCD4 were investigated by luciferase reporter assay, real-time PCR and Western blotting.

Results

We found that miR-202 is overexpressed in osteosarcoma tissues when compared with normal human osteoblasts and TGF-β1 can induce the expression of miR-202. Transfection of miR-202 mimics into osteosarcoma cell lines significantly promotes chemotherapy resistance by targeting PDCD4, a tumor suppressor which is involved in apoptosis. In contrast, transfection of miR-202 inhibitor enhances the drug sensitivity and apoptosis.

Conclusions

This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy.

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Authors and Affiliations

  1. Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China

    Zaijun Lin, Dianwen Song, Haifeng Wei, Xinghai Yang, Tielong Liu, Wangjun Yan & Jianru Xiao

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  1. Zaijun Lin
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  2. Dianwen Song
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  3. Haifeng Wei
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  4. Xinghai Yang
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  5. Tielong Liu
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  6. Wangjun Yan
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  7. Jianru Xiao
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Corresponding author

Correspondence to Jianru Xiao.

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Conflict of interest

The authors declare no conflict of interest.

Ethical standards

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

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Cite this article

Lin, Z., Song, D., Wei, H. et al. TGF-β1-induced miR-202 mediates drug resistance by inhibiting apoptosis in human osteosarcoma. J Cancer Res Clin Oncol 142, 239–246 (2016). https://doi.org/10.1007/s00432-015-2028-9

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  • DOI: https://doi.org/10.1007/s00432-015-2028-9

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