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Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma

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Abstract

Purpose

Bladder cancer is the most general malignant cancer in genitourinary system, more than 90% of BCs are bladder transitional cell carcinomas (BTCC). This study aimed to investigate the clinical significance of growth arrest-specific 5 (GAS5) gene and its regulatory effects of malignant proliferation and chemotherapy resistance to doxorubicin in BTCC cells.

Methods

The expression of GAS5 was detected by quantitative real-time PCR. Statistical analysis was used to determine the relationship between GAS5 expression and clinical features and the prognostic value of GAS5 for disease free survival. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis. The expression of Bcl-2 protein was examined by western blot.

Results

In this study, we found that GAS5 low-expressed in BTCC tissues and cells, and its low expression level had positive correlation with higher pathological grades of BTCC. Moreover, GAS5 was a prognostic biomarker of disease free survival for BTCC patients. GAS5 over-expression could inhibit cell proliferation of BTCC J82 and T24 cells significantly. The IC50 to doxorubicin in T24/DOX cells (resistance to doxorubicin) presented a conspicuous depression, GAS5 enhancement reduced the chemotherapy resistance to doxorubicin. GAS5 over-expression promoted apoptosis induced by doxorubicin in T24/DOX cells, and depressed the expression of anti-apoptosis protein Bcl-2. The results indicated that GAS5 regulated the chemotherapy resistance to doxorubicin via Bcl2 partly.

Conclusions

In summary, lncRNA GAS5 was a prognostic biomarker of disease free survival in BTCC patients, and acted as a tumor-suppressing gene to inhibit malignant proliferation and resistance to doxorubicin in BTCC cells. LncRNA GAS5 might be a novel potential therapeutic target for BTCC.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (81301834, 81172408, 30901480, 81272716).

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Authors and Affiliations

  1. Department of Urinary Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China

    Hui Zhang & Yongsheng Song

  2. Department of Central Laboratory, School of Stomatology, China Medical University, Shenyang, 110007, China

    Yan Guo

  3. Department of Neurobiology, College of Basic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China

    Chao Shang

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  1. Hui Zhang
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  2. Yan Guo
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  3. Yongsheng Song
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  4. Chao Shang
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Correspondence to Chao Shang.

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Zhang, H., Guo, Y., Song, Y. et al. Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma. Cancer Chemother Pharmacol 79, 49–55 (2017). https://doi.org/10.1007/s00280-016-3194-4

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  • DOI: https://doi.org/10.1007/s00280-016-3194-4

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