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Long non-coding RNA GHET1 contributes to chemotherapeutic resistance to Gemcitabine in bladder cancer

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Abstract

Purpose

Bladder cancer (BC) ranks first in the incidence of urogenital tumors in China and second only to prostate cancer in the West. This study will clarify the roles and mechanism of lncRNA GHET1 in chemotherapeutic resistance of BC to Gemcitabine.

Methods

The expression of GHET1 was examined using real-time quantitative PCR. Cell Counting Kit-8 assay was applied to analyze cell proliferation and Gemcitabine sensitivity. Cell apoptosis was detected using Annexin V-FITC/PI double-stained flow cytometry. The expression of ABCC1 protein was examined using Western blotting.

Results

Firstly, the expression of GHET1 was up-regulated in BC, its high expression was relevant to high grade and muscle invasion of BC patients. Secondly, high expression of GHET1 was related to low Gemcitabine sensitivity of BC patients, and GHET1 was highly expressed in Gemcitabine-resistant BC cell lines. Thirdly, knockdown of GHET1 decreased the IC50 of Gemcitabine in Gemcitabine-resistant BC cell lines and advanced the Gemcitabine-induced cytotoxicity; GHET1 promoted Gemcitabine resistance in BC. Finally, knockdown of GHET1 also inhibited the expression of ABCC1 protein in Gemcitabine-resistant BC cells.

Conclusions

High expression of GHET1 was related with the low sensitivity to Gemcitabine of BC; GHET1 contributed to chemotherapeutic resistance to Gemcitabine in BC through up-regulating ABCC1 expression. Our findings are helpful to expound the molecular mechanism of chemotherapeutic resistance in BC.

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (Grant Nos. 81872067, 30901480, 81301834).

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Authors and Affiliations

  1. Department of Urinary Surgery, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping Area, Shenyang, 100004, China

    Bo Li & Hui Zhang

  2. Department of Anatomy, College of Basic Medical Science, China Medical University, Shenyang, 110001, China

    Dalon Xie

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  1. Bo Li
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  2. Dalon Xie
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  3. Hui Zhang
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Contributions

ZL and DX carried out the experiments and performed the statistical analysis. HZ participated in the study design and drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hui Zhang.

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Li, B., Xie, D. & Zhang, H. Long non-coding RNA GHET1 contributes to chemotherapeutic resistance to Gemcitabine in bladder cancer. Cancer Chemother Pharmacol 84, 187–194 (2019). https://doi.org/10.1007/s00280-019-03873-8

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  • DOI: https://doi.org/10.1007/s00280-019-03873-8

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