Lung Cancer
Volume 72, Issue 1 , Pages 92-99, April 2011

Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer☆

  • Xiao-Chun Wang

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • These authors contributed equally to this work.
    • ,
  • Li-Qing Du

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • These authors contributed equally to this work.
    • ,
  • Li-Li Tian

      Affiliations

    • Institute of Infectious and Endemic Disease Prevention, Beijing Centers for Disease Control and Prevention, Beijing 100013, China
    • These authors contributed equally to this work.
    • ,
  • Hai-Liang Wu

      Affiliations

    • Department of Tumor Medicine, Shandong Provincial Chest Hospital, Jinan 250013, China
    • ,
  • Xiao-Yan Jiang

      Affiliations

    • Department of Policy and Standard Research, The National Institute for Radiological Protection and Nuclear Safety, Chinese Centre for Disease Control and Prevention, Beijing 100050, China
    • ,
  • Heng Zhang

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • ,
  • De-Guan Li

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • ,
  • Yue-Ying Wang

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • ,
  • Hong-Ying Wu

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • ,
  • Yi She

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • ,
  • Qing-fen Liu

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • ,
  • Fei-Yue Fan

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • Tel.: +86 022 85683036.
    • Corresponding Author InformationCorresponding author. Tel.: +86 022 85683043; fax: +86 022 85683043.
    • ,
  • Ai-Min Meng

      Affiliations

    • Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
    • Corresponding Author InformationCorresponding author. Tel.: +86 022 85683043; fax: +86 022 85683043.

Received 7 February 2010; received in revised form 13 July 2010; accepted 29 July 2010. published online 23 August 2010.

Abstract 

Purpose

To investigate the different miRNA expression profiles of postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, explore their potential role and find some radio-sensitivity markers.

Materials and methods

Thirty non-small cell lung cancer patients who have been treated by postoperative radiotherapy were selected and were divided into radiotherapy sensitive group and resistant group according to overall survival and local or distant recurrence rate. Expression profile of miRNA in these two groups was detected by a microarray assay and the results were validated by quantitative RT-PCR and Northern blot. At the molecular level, the effect of one differently expressed miRNA (miR-126) on the growth and apoptosis of SK-MES-1 cells induced by irradiation was examined.

Results

Comparing with resistant patients, five miRNAs (miRNA-126, miRNA-let-7a, miRNA-495, miRNA-451 and miRNA-128b) were significantly upregulated and seven miRNAs (miRNA-130a, miRNA-106b, miRNA-19b, miRNA-22, miRNA-15b, miRNA-17-5p and miRNA-21) were greatly downregulated in radiotherapy sensitive group. Overexpression of miRNA-126 inhibited the growth of SK-MES-1 cells and promoted its apoptosis induced by irradiation. The expression level of p-Akt decreased in miRNA-126 overexpression group. After treating with phosphoinositidyl-3 kinase (PI3K) constitutively activator (IGF-1) and inhibitor (LY294002), miRNA-126 overexpression had no significant effects on the apoptosis of SK-MES-1 cells.

Conclusion

We found 12 differently expressed miRNAs in the radiotherapy sensitive and resistant non-small cell lung cancer samples. Moreover, our results showed miRNA-126 promoted non-small cell lung cancer cells apoptosis induced by irradiation through the PI3K-Akt pathway.

Keywords: miRNA, Radiotherapy sensitivity, Apoptosis, NSCLC

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☆ Grant support: National Natural Science Foundation of China (30901723), Research Fund for the Doctoral Program of Higher Education of China (200800231052), Natural Science Foundation of Tianjin (08JCYBJC07300), CMB (A2009002) and Institute fund of Radiation Medicine (SR0815).

PII: S0169-5002(10)00377-6

doi:10.1016/j.lungcan.2010.07.014

Lung Cancer
Volume 72, Issue 1 , Pages 92-99, April 2011

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