PMID- 31894344
OWN - NLM
STAT- MEDLINE
DCOM- 20200821
LR  - 20211112
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 43
IP  - 2
DP  - 2020 Feb
TI  - Effect of CUL4A on the metastatic potential of lung adenocarcinoma to the bone.
PG  - 662-670
LID - 10.3892/or.2019.7448 [doi]
AB  - Cullin 4A (CUL4A) is a member of the cullin family of proteins and has been 
      demonstrated to be abnormally expressed in various types of malignancies. 
      However, the function of CUL4A in metastasis of lung adenocarcinoma to the bone 
      has rarely been reported. The aim of present of the study was to explore the 
      biological functions and potential underlying molecular mechanisms of CUL4A in 
      lung adenocarcinoma, highlighting a novel therapeutic target for the diagnosis 
      and treatment of patients with lung adenocarcinoma. A549‑CUL4A, H1299‑CUL4A and 
      H460‑shCUL4A cells were created using lentiviral infection. The efficiency of 
      knockdown or overexpression was assessed using reverse transcription‑quantitative 
      PCR and western blotting. The effects of CUL4A on proliferation, migration and 
      invasion of lung adenocarcinoma cells in vitro and metastasis to the bone in vivo 
      were determined using an MTT assay, colony formation assay, wound‑healing assay, 
      Transwell assay and a mouse model of bone metastasis. The relationship between 
      CUL4A and the EMT‑activator zinc finger E‑box binding homeobox 1 (ZEB1) were 
      detected by western blotting. The results showed that overexpression of CUL4A in 
      lung adenocarcinoma cells increased proliferation, migration and invasion, and 
      increased metastasis of A549 to the bones in vivo. Silencing of CUL4A expression 
      in lung adenocarcinoma cells reduced proliferation, migration and invasion 
      in vitro. Mechanistically, CUL4A transcriptionally upregulated expression of ZEB1 
      which resulted in epithelial‑mesenchymal transition, which in turn promoted 
      metastasis of lung adenocarcinoma to the bones. Taken together, these results 
      suggest that CUL4A may serve an important regulatory role in the development of 
      metastasis of lung adenocarcinoma to the bone.
FAU - Cao, Pei-Pei
AU  - Cao PP
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
FAU - Chen, Wen-Juan
AU  - Chen WJ
AD  - Department of Oncology, Tumor Hospital of Shaanxi Province, Xi'an, Shaanxi 
      710061, P.R. China.
FAU - Pang, Hai-Lin
AU  - Pang HL
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
FAU - Shen, Wei-Wei
AU  - Shen WW
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
FAU - Xue, Peng
AU  - Xue P
AD  - Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 
      Shaanxi 710054, P.R. China.
FAU - Duan, Lian
AU  - Duan L
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
FAU - Xu, Yu-Xuan
AU  - Xu YX
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
FAU - Liu, Li-Li
AU  - Liu LL
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
FAU - Zhang, He-Long
AU  - Zhang HL
AD  - Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, 
      Shaanxi 710038, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20191227
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (ZEB1 protein, human)
RN  - 0 (Zinc Finger E-box-Binding Homeobox 1)
SB  - IM
MH  - A549 Cells
MH  - Adenocarcinoma of Lung/genetics/metabolism/*pathology
MH  - Animals
MH  - Bone Neoplasms/genetics/metabolism/*pathology/*secondary
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cullin Proteins/*genetics/*metabolism
MH  - Epithelial-Mesenchymal Transition
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/genetics/metabolism/*pathology
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Up-Regulation
MH  - Zinc Finger E-box-Binding Homeobox 1/*genetics
OTO - NOTNLM
OT  - CUL4A
OT  - cullin 4A
OT  - lung adenocarcinoma
OT  - ZEB1
OT  - epithelial-mesenchymal transition
OT  - bone metastasis
EDAT- 2020/01/03 06:00
MHDA- 2020/08/22 06:00
CRDT- 2020/01/03 06:00
PHST- 2019/06/28 00:00 [received]
PHST- 2019/11/27 00:00 [accepted]
PHST- 2020/01/03 06:00 [pubmed]
PHST- 2020/08/22 06:00 [medline]
PHST- 2020/01/03 06:00 [entrez]
AID - 10.3892/or.2019.7448 [doi]
PST - ppublish
SO  - Oncol Rep. 2020 Feb;43(2):662-670. doi: 10.3892/or.2019.7448. Epub 2019 Dec 27.