PMID- 32165307
OWN - NLM
STAT- MEDLINE
DCOM- 20200518
LR  - 20200518
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 747
DP  - 2020 Jul 15
TI  - TRIM59 knockdown blocks cisplatin resistance in A549/DDP cells through regulating 
      PTEN/AKT/HK2.
PG  - 144553
LID - S0378-1119(20)30222-5 [pii]
LID - 10.1016/j.gene.2020.144553 [doi]
AB  - Cisplatin is commonly used for lung cancer treatment. However, acquire resistance 
      to cisplatin results in reduced therapy efficacy. Tripartite motif-containing 59 
      (TRIM59), acting as an oncogene in non-small cell lung cancer (NSCLC), induces 
      chemoresistance in breast cancer cells. Here, the mechanism by which TRIM59 
      mediates cisplatin resistance was determined. We demonstrated that 
      cisplatin-resistant NSCLC cell line (A549/DDP) had higher expression of TRIM59 
      than its parental cell line (A549). As indicated by cell apoptosis assay, TRIM59 
      overexpression in A549 cells resulted in an increased cisplatin resistance, while 
      TRIM59 downregulation in A549/DDP cells led to an decreased cisplatin resistence. 
      A549/DDP cells with TIMR59 knockdown was more sensitive to cisplatin treatment in 
      a xenograft model. Moreover, A549/DDP cells exhibited increased glucose uptake, 
      lactate production, and hexokinase 2 (HK2, an important glycolytic pathway 
      enzyme) expression than A549 cells. The glycolysis was increased by TRIM59 
      overexpression in A549 cell, and decreased by TRIM59 knockdown in A549/DDP cells. 
      3-Bromopyruvate Acid (3-BrPA), an inhibitor of HK2, significantly enhanced 
      cisplatin-sensitivity in A549 cells overexpressing TRIM59. Furthermore, both 
      TRIM59 and HK2 expression was higher in cisplatin-resistant NSCLC tissues than in 
      non-resistant ones, and mRNA expression of these two molecules was positively 
      correlated in NSCLC tissues. The changes of PTEN and phosphorylation of AKT 
      (p-AKT), a critical upstream regulator of HK2, were also consistent with HK2 
      expression. Immunoprecipiation experiments showed the interaction between TRIM59 
      and PTEN in A549/DDP cells, and that TRIM59 knockdown suppressed the 
      ubiquitination of PTEN. Collectively, the present study indicates that TRIM59 
      knockdown reverses high glycolysis rate and cisplatin resistance in A549/DDP 
      cells through the regulation of PTEN/AKT/HK2 and may provide insights into 
      overcoming cancer resistance to cisplatin treatment.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - He, Rong
AU  - He R
AD  - Department of Thoracic Oncology, Cancer Hospital of China Medical University, 
      Liaoning Cancer Hospital & Institute, PR China.
FAU - Liu, Hongxu
AU  - Liu H
AD  - Department of Thoracic Oncology, Cancer Hospital of China Medical University, 
      Liaoning Cancer Hospital & Institute, PR China. Electronic address: 
      lhx2134@sohu.com.
LA  - eng
PT  - Journal Article
DEP - 20200309
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TRIM59 protein, human)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Carcinoma, Non-Small-Cell Lung/genetics/pathology
MH  - Cisplatin/*pharmacology
MH  - Down-Regulation/drug effects/genetics
MH  - *Drug Resistance, Neoplasm/drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - *Gene Knockdown Techniques
MH  - Glycolysis/drug effects/genetics
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Lung Neoplasms/genetics/pathology
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Tripartite Motif Proteins/*metabolism
MH  - Ubiquitination
OTO - NOTNLM
OT  - Cisplatin resistance
OT  - Glycolysis
OT  - NSCLC
OT  - TRIM59
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/03/14 06:00
MHDA- 2020/05/19 06:00
CRDT- 2020/03/14 06:00
PHST- 2019/07/11 00:00 [received]
PHST- 2020/03/08 00:00 [accepted]
PHST- 2020/03/14 06:00 [pubmed]
PHST- 2020/05/19 06:00 [medline]
PHST- 2020/03/14 06:00 [entrez]
AID - S0378-1119(20)30222-5 [pii]
AID - 10.1016/j.gene.2020.144553 [doi]
PST - ppublish
SO  - Gene. 2020 Jul 15;747:144553. doi: 10.1016/j.gene.2020.144553. Epub 2020 Mar 9.