PMID- 30015884 OWN - NLM STAT- MEDLINE DCOM- 20181026 LR - 20181114 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 18 IP - 3 DP - 2018 Sep TI - Investigation of the role of cullin 4A overexpression in human liver cancer. PG - 2531-2540 LID - 10.3892/mmr.2018.9233 [doi] AB - Cullin 4A (CUL4A) is the major component of cullin‑RING‑based E3 ubiquitin‑protein ligase complexes, which regulate the ubiquitination of target proteins. The overexpression of CUL4A has been associated with the development and progression of various cancer types. However, a detailed understanding of the role of CUL4A in human liver cancer has not been determined by previous studies. In the present study, the association between human liver cancer and CUL4A expression was investigated. The expression of CUL4A in liver cancer tissues and paracancerous tissues of patients was investigated by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemical staining. Overexpression and knockdown of CUL4A were induced with an overexpression vector and small interfering RNA transfection, respectively, in human liver cancer cell lines, and the effects on cell proliferation were analyzed by a Cell Counting Kit‑8 assay to investigate the role of CUL4A in human liver cancer. Cell migration, invasion, apoptosis and the cell cycle were also analyzed following transfection. The results of the present study revealed that the mRNA and protein expression of CUL4A was increased in the liver cancer tissues compared with the paracancerous tissues of 3 patients. Additionally, the results demonstrated that downregulation of CUL4A expression inhibited cell proliferation, migration and invasion, and increased the percentage of cell apoptosis, in HEPG2 and MHCC97‑H cells, while CUL4A overexpression led to the opposite effects. Therefore, the results of the current study indicated that CUL4A may serve an important role in the development and progression of human liver cancer, and highlights the potential of CUL4A as a novel target in the diagnosis and treatment of human liver cancer and potentially other cancer types. FAU - Chen, Gang AU - Chen G AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Zhao, Xiongqi AU - Zhao X AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Tan, Zedan AU - Tan Z AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Wang, Dongdong AU - Wang D AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Luo, Ding AU - Luo D AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Zhang, Peiyao AU - Zhang P AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Cao, Jun AU - Cao J AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Wang, Fan AU - Wang F AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Liu, Qiyu AU - Liu Q AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. FAU - Li, Li AU - Li L AD - Department of Hepatobiliary Surgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China. LA - eng PT - Journal Article DEP - 20180629 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (CUL4A protein, human) RN - 0 (Cadherins) RN - 0 (Claudin-3) RN - 0 (Cullin Proteins) RN - 0 (Occludin) RN - 0 (RNA, Small Interfering) SB - IM MH - Apoptosis MH - Cadherins/metabolism MH - Cell Cycle Checkpoints MH - Cell Line, Tumor MH - Cell Movement MH - Claudin-3/metabolism MH - Cullin Proteins/antagonists & inhibitors/genetics/*metabolism MH - Hep G2 Cells MH - Humans MH - Liver/metabolism/pathology MH - Liver Neoplasms/metabolism/*pathology MH - Occludin/metabolism MH - RNA Interference MH - RNA, Small Interfering/metabolism PMC - PMC6102737 EDAT- 2018/07/18 06:00 MHDA- 2018/10/27 06:00 PMCR- 2018/06/29 CRDT- 2018/07/18 06:00 PHST- 2017/09/15 00:00 [received] PHST- 2018/01/09 00:00 [accepted] PHST- 2018/07/18 06:00 [pubmed] PHST- 2018/10/27 06:00 [medline] PHST- 2018/07/18 06:00 [entrez] PHST- 2018/06/29 00:00 [pmc-release] AID - mmr-18-03-2531 [pii] AID - 10.3892/mmr.2018.9233 [doi] PST - ppublish SO - Mol Med Rep. 2018 Sep;18(3):2531-2540. doi: 10.3892/mmr.2018.9233. Epub 2018 Jun 29.