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Mechanisms underlying regulation of cell cycle and apoptosis by hnRNP B1 in human lung adenocarcinoma A549 cells

Abstract

Aims and background. Overexpression of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1), a nuclear RNA binding protein, has been reported to occur in earlystage lung cancer and in premalignant lesions. DNA-dependent protein kinase (DNAPK) is known to be involved in the repair of double-strand DNA breaks. Reduced capacity to repair DNA has been associated with the risk of lung cancer.
Methods and study design. We investigated a link between hnRNP B1 and DNA-PK and their effects on proliferation, cell cycle, and apoptosis in the human lung adenocarcinoma cell line A549.
Results. We found that hnRNP B1 and DNA-PK interact with each other in a complex fashion. Reducing hnRNP B1 expression in A549 cells with the use of RNAi led to upregulation of p53 activity through upregulation of DNA-PK activity but without inducing p53 expression. Further, suppression of hnRNP B1 in A549 cells slowed cell proliferation, promoted apoptosis, and induced cell cycle arrest at the G1 stage. The presence of NU7026 reduced the arrest of cells at the G1 stage and reduced the apoptosis rate while promoting cell growth.
Conclusion. Taken together, our results demonstrate that by regulating DNA-PK activity, hnRNP B1 can affect p53-mediated cell cycle progression and apoptosis, resulting in greater cell survival and subsequent proliferation.

Tumori 2014; 100(1): 102 - 111

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.1700/1430.15824

Authors

Juan Han, Feng-ming Tang, Dan Pu, Dan Xu, Tao Wang, Weimin Li

Article History

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Authors

  • Han, Juan [PubMed] [Google Scholar]
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
  • Tang, Feng-ming [PubMed] [Google Scholar]
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
  • Pu, Dan [PubMed] [Google Scholar]
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
  • Xu, Dan [PubMed] [Google Scholar]
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
  • Wang, Tao [PubMed] [Google Scholar]
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
  • Li, Weimin [PubMed] [Google Scholar]
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China

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