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Article

Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells

  • Authors:
    • Yong Li
    • Wei Han
    • Ting-Ting Ni
    • Liang Lu
    • Min Huang
    • Yu Zhang
    • Hui Cao
    • Han-Qun Zhang
    • Wen Luo
    • Hang Li
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Department of Occupational and Environmental Health, School of Public Health, Ningxia Medical University, Ningxia 750004, P.R. China
  • Pages: 2821-2828
    |
    Published online on: March 30, 2015
       https://doi.org/10.3892/or.2015.3884
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Abstract

Resistance to radiation is a major problem in cancer treatment. The mechanisms of radioresistance remain poorly understood; however, mounting evidence supports a role for microRNAs (miRNAs) in the modulation of key cellular pathways mediating the response to radiation. The present study aimed to identify specific miRNAs and their effect on radioresistant cells. The global miRNA profile of an established radioresistant lung cancer cell line and the corresponding control cells was determined. Differential expression of the miRNAs was confirmed by quantitative real-time PCR (qRT‑PCR). The binding effect of identical novel miRNAs and target mRNAs was determined by luciferase assay. Lung cancer cells were transfected with miRNA-specific mimics or inhibitors. The DNA-dependent protein kinase (DNA-PKcs) protein level was tested by western blot analysis. Radiosensitivity of cancer cells was determined using colony formation assay. Among the differentially expressed miRNAs, 25 miRNAs were overexpressed while 18 were suppressed in the radioresistant cells, both basally and in response to radiation compared to their control. An miRNA signature miR-1323 exhibited a >5-fold increase in the radioresistant cells. miR-1323 was demonstrated to bind to PRKDC 3'UTR, which is involved in DNA repair. Ectopic expression of miR-1323 significantly increased the survival fraction of irradiated cancer cells. Inhibition of miR-1323 reversed the radioresistance of cancer cells and subsequently suppressed the expression of miR‑1323-regulated DNA-PKcs protein. The present study indicated that miRNAs are involved in the radioresistance of human lung cancer cells. A possible mechanism for resistance to radiation was via enhanced DNA repair. The present study demonstrated a role for miR-1323 in modulating radioresistance and highlights the need for further study investigating the potential role of miR-1323 as both a predictive marker of response and a novel therapeutic agent with which to enhance the efficacy of radiotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Han W, Ni T, Lu L, Huang M, Zhang Y, Cao H, Zhang H, Luo W, Li H, Li H, et al: Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells. Oncol Rep 33: 2821-2828, 2015.
APA
Li, Y., Han, W., Ni, T., Lu, L., Huang, M., Zhang, Y. ... Li, H. (2015). Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells. Oncology Reports, 33, 2821-2828. https://doi.org/10.3892/or.2015.3884
MLA
Li, Y., Han, W., Ni, T., Lu, L., Huang, M., Zhang, Y., Cao, H., Zhang, H., Luo, W., Li, H."Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells". Oncology Reports 33.6 (2015): 2821-2828.
Chicago
Li, Y., Han, W., Ni, T., Lu, L., Huang, M., Zhang, Y., Cao, H., Zhang, H., Luo, W., Li, H."Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells". Oncology Reports 33, no. 6 (2015): 2821-2828. https://doi.org/10.3892/or.2015.3884
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Han W, Ni T, Lu L, Huang M, Zhang Y, Cao H, Zhang H, Luo W, Li H, Li H, et al: Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells. Oncol Rep 33: 2821-2828, 2015.
APA
Li, Y., Han, W., Ni, T., Lu, L., Huang, M., Zhang, Y. ... Li, H. (2015). Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells. Oncology Reports, 33, 2821-2828. https://doi.org/10.3892/or.2015.3884
MLA
Li, Y., Han, W., Ni, T., Lu, L., Huang, M., Zhang, Y., Cao, H., Zhang, H., Luo, W., Li, H."Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells". Oncology Reports 33.6 (2015): 2821-2828.
Chicago
Li, Y., Han, W., Ni, T., Lu, L., Huang, M., Zhang, Y., Cao, H., Zhang, H., Luo, W., Li, H."Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells". Oncology Reports 33, no. 6 (2015): 2821-2828. https://doi.org/10.3892/or.2015.3884
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