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Article

Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2

  • Authors:
    • Baohong Jiang
    • Yuehua Li
    • Xiaofei Qu
    • Hongbo Zhu
    • Yeru Tan
    • Qun Fan
    • Yiling Jiang
    • Mingchu Liao
    • Xiaoping Wu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
  • Pages: 2801-2810
    |
    Published online on: August 7, 2018
       https://doi.org/10.3892/ijmm.2018.3812
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Abstract

The present study aimed to investigate the effect of the long noncoding RNA cancer susceptibility candidate 9 (CASC9) on doxorubicin (DOX)‑resistant breast cancer and to reveal the potential underlying mechanisms. The expression of CASC9 in breast cancer tissues and cell lines, in addition to drug‑resistant breast cancer cells (MCF‑7/DOX), was detected by reverse transcription‑quantitative polymerase chain reaction. Subsequently, MCF‑7/DOX cells were transfected with the silencing vector pS‑CASC9, containing enhancer of zeste homolog 2 (EZH2), multidrug resistance protein 1 (MDR1) or control small interfering (si)RNAs. The viability, apoptosis, migration and invasion of the transfected cells were assessed via an MTT assay, flow cytometry and a Transwell assay, respectively. The expression levels of apoptosis‑associated proteins (apoptosis regulator Bcl‑2, apoptosis regulator BAX, caspase‑3 and caspase‑9) were determined by western blotting. An RNA pull‑down assay was performed to identify CASC9‑binding candidates. In addition, the expression levels of the MDR1 gene and its encoded protein, P‑glycoprotein, were detected. CASC9 expression was upregulated in breast cancer tissues and cell lines, and drug‑resistant breast cancer cells. CASC9 knockdown significantly inhibited the growth and metastasis of drug‑resistant breast cancer cells, and decreased the half‑maximal inhibitory concentration DOX in MCF‑7/DOX cells. The RNA pull‑down assay revealed that CASC9 engaged EZH2; EZH2 siRNA significantly inhibited the cell growth, metastasis and chemoresistance of MCF‑7/DOX cells. Additionally, EZH2 may regulate the MDR1 gene. The present study demonstrated the oncogenic role of CASC9 in drug‑resistant breast cancer by binding to EZH2 and regulating the MDR1 gene. Modulation of CASC9 expression may be a promising target in the therapy of breast cancer and drug‑resistant breast cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang B, Li Y, Qu X, Zhu H, Tan Y, Fan Q, Jiang Y, Liao M and Wu X: Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2. Int J Mol Med 42: 2801-2810, 2018.
APA
Jiang, B., Li, Y., Qu, X., Zhu, H., Tan, Y., Fan, Q. ... Wu, X. (2018). Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2. International Journal of Molecular Medicine, 42, 2801-2810. https://doi.org/10.3892/ijmm.2018.3812
MLA
Jiang, B., Li, Y., Qu, X., Zhu, H., Tan, Y., Fan, Q., Jiang, Y., Liao, M., Wu, X."Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2". International Journal of Molecular Medicine 42.5 (2018): 2801-2810.
Chicago
Jiang, B., Li, Y., Qu, X., Zhu, H., Tan, Y., Fan, Q., Jiang, Y., Liao, M., Wu, X."Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2". International Journal of Molecular Medicine 42, no. 5 (2018): 2801-2810. https://doi.org/10.3892/ijmm.2018.3812
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang B, Li Y, Qu X, Zhu H, Tan Y, Fan Q, Jiang Y, Liao M and Wu X: Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2. Int J Mol Med 42: 2801-2810, 2018.
APA
Jiang, B., Li, Y., Qu, X., Zhu, H., Tan, Y., Fan, Q. ... Wu, X. (2018). Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2. International Journal of Molecular Medicine, 42, 2801-2810. https://doi.org/10.3892/ijmm.2018.3812
MLA
Jiang, B., Li, Y., Qu, X., Zhu, H., Tan, Y., Fan, Q., Jiang, Y., Liao, M., Wu, X."Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2". International Journal of Molecular Medicine 42.5 (2018): 2801-2810.
Chicago
Jiang, B., Li, Y., Qu, X., Zhu, H., Tan, Y., Fan, Q., Jiang, Y., Liao, M., Wu, X."Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2". International Journal of Molecular Medicine 42, no. 5 (2018): 2801-2810. https://doi.org/10.3892/ijmm.2018.3812
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