TY - JOUR T1 - Knockdown of Cul4A increases chemosensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells. JF - Oncol Rep Y1 - 2015 A1 - Hung, Ming-Szu A1 - Chen, I-Chuan A1 - You, Liang A1 - Jablons, David M A1 - Li, Ya-Chin A1 - Jiang-Hua Mao A1 - Xu, Zhidong A1 - Hsieh, Meng-Jer A1 - Lin, Yu-Ching A1 - Yang, Cheng-Ta A1 - Liu, Shin-Tung A1 - Tsai, Ying-Huang KW - Animals KW - Cell Line, Tumor KW - Cell Transformation, Neoplastic KW - Cullin Proteins KW - Deoxycytidine KW - Drug Resistance, Neoplasm KW - Extracellular Matrix Proteins KW - Gene Expression Regulation, Neoplastic KW - Gene Knockdown Techniques KW - Humans KW - Lung Neoplasms KW - Mice KW - Transforming Growth Factor beta KW - Xenograft Model Antitumor Assays AB -

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.

VL - 34 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26503734?dopt=Abstract ER -