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

TitleKnockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsHung M-S, Chen I-C, You L, Jablons DM, Li Y-C, Mao J-H, Xu Z, Lung J-H, Yang C-T, Liu S-T
JournalJ Cell Mol Med
Volume20
Issue7
Pagination1295-306
Date Published2016 Jul
ISSN1582-4934
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)-β 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.

DOI10.1111/jcmm.12811
Alternate JournalJ. Cell. Mol. Med.
PubMed ID26969027
PubMed Central IDPMC4929302