Knockdown of Cul4A increases chemosensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells | Zendy

MingSzu Hung | Zendy; IChuan Chen | Zendy; Liang You | Zendy; David M. Jablons | Zendy; YaChin Li | Zendy; JianHua Mao | Zendy; Zhidong Xu | Zendy; MengJer Hsieh | Zendy; YuChing Lin | Zendy; ChengTa Yang | Zendy; ShihTung Liu | Zendy; YingHuang Tsai | Zendy

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Knockdown of Cul4A increases chemosensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells

Author(s) -

MingSzu Hung,

IChuan Chen,

Liang You,

David M. Jablons,

YaChin Li,

JianHua Mao,

Zhidong Xu,

MengJer Hsieh,

YuChing Lin,

ChengTa Yang,

ShihTung Liu,

YingHuang Tsai

Publication year - 2015

Publication title -

oncology reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.094

H-Index - 96

eISSN - 1791-2431

pISSN - 1021-335X

DOI - 10.3892/or.2015.4324

Subject(s) - cancer research , gene knockdown , gemcitabine , tgfbi , oncogene , biology , pancreatic cancer , rna interference , cullin , carcinogenesis , transfection , downregulation and upregulation , cell cycle , cancer , ubiquitin ligase , ubiquitin , cell culture , microbiology and biotechnology , transforming growth factor , gene , rna , biochemistry , genetics

Cullin 4A (Cul4A) promotes oncogenesis through overexpression and then ubiquitination‑mediated proteolysis of tumor suppressors in various types of cancers. Transforming growth factor β‑induced (TGFBI) has been implicated as a tumor suppressor, which enhances gemcitabine chemosensitivity in lung cancer cells. The present study aimed to investigate the association of TGFBI and Cul4A and the mechanism by which Cul4A regulates TGFBI. In addition, we also evaluated the therapeutic value of Cul4A RNAi using adenoviral transfection of Cul4A RNAi in nude mouse xenograft models. We observed that knockdown of Cul4A was associated with increased sensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells. Cul4A regulated TGFBI through direct interaction and then ubiquitin‑mediated protein degradation. In the nude mouse xenograft models, adenoviral transfection of Cul4A RNAi in combination with gemcitabine chemotherapy inhibited lung cancer tumor growth. As the result, combination of Cul4A RNAi with chemotherapy may provide a new approach to lung cancer treatment.

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