Silencing tankyrase and telomerase promotes A549 human lung adenocarcinoma cell apoptosis and inhibits proliferation

Lu,Hongda; Lei,Zhang; Lu,Zhongxin; Lu,Qianming; Lu,Chi; Chen,Weiqun; Wang,Chun; Tang,Qiu; Kong,Qingzhi

doi:10.3892/or.2013.2665

October 2013 Volume 30 Issue 4

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October 2013 Volume 30 Issue 4

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Article

Silencing tankyrase and telomerase promotes A549 human lung adenocarcinoma cell apoptosis and inhibits proliferation

Authors:
- Hongda Lu
- Zhang Lei
- Zhongxin Lu
- Qianming Lu
- Chi Lu
- Weiqun Chen
- Chun Wang
- Qiu Tang
- Qingzhi Kong
View Affiliations / Copyright

Affiliations: Department of Oncology, the Central Hospital of Wuhan, Wuhan, Hubei, P.R. China, Cancer Research Institute of Wuhan, Wuhan, Hubei, P.R. China
Pages: 1745-1752
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Published online on: August 8, 2013

https://doi.org/10.3892/or.2013.2665
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Abstract

Telomeres are the end structures of chromosomes in mammalian cells; they play a pivotal role in maintaining the stability of the chromosome and become shorter with each cell division. However, several types of tumor cells express telomerase in very high levels to overcome this crisis and achieve the ability to proliferate endlessly. The telomerase inhibitors can partly inhibit tumor cell proliferation and promote apoptosis, but their roles are only limited. Tankyrase is a poly(ADP-ribose) polymerase which has synergistic effect on telomerase, and is expressed in lung cancer cells in high levels. In the present study, antisense oligonucleotides of telomerase (ashTERT) and tankyrase (asTANKS) were used as specific inhibitors to silence the expression of target genes in A549 human lung adenocarcinoma cells by transfection. The results showed that ashTERT and asTANKS suppressed the expression of telomerase and tankyrase significantly; both inhibited the activity of telomerase and the combination group achieved better effect, but only ashTERT shortened the length of telomeres, asTANKS did not. Further studies showed that ashTERT and asTANKS-promoted A549 apoptosis was not mediated by downregulation of the expression of the anti‑apoptotic gene BCL-2 or upregulation of the expression of the pro‑apoptotic gene BAX, but by adjusting the two isoforms proportion of myeloid cell leukemia-1 (MCL‑1) which can interact with tankyrase directly. MCL-1short (MCL‑1S), a pro-apoptotic gene, increased more than MCL-1Long (MCL‑1L) which is an anti-apoptotic gene, leading to A549 cell apoptosis and a similar result was obtained in nude mice in vivo. The present study suggests that combination of the inhibitors of telomerase and tankyrase can be used as a strategy for the treatment of lung cancer in humans.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Silencing tankyrase and telomerase promotes A549 human lung adenocarcinoma cell apoptosis and inhibits proliferation

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