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Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.


ABSTRACT: Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-? inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future.

SUBMITTER: Hung MS 

PROVIDER: S-EPMC4929302 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

Hung Ming-Szu MS   Chen I-Chuan IC   You Liang L   Jablons David M DM   Li Ya-Chin YC   Mao Jian-Hua JH   Xu Zhidong Z   Lung Jr-Hau JH   Yang Cheng-Ta CT   Liu Shih-Tung ST  

Journal of cellular and molecular medicine 20160310 7


Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung can  ...[more]

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