PMID- 33662669
OWN - NLM
STAT- MEDLINE
DCOM- 20210908
LR  - 20210908
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 549
DP  - 2021 Apr 16
TI  - miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in 
      lung adenocarcinoma cell line A549.
PG  - 54-60
LID - S0006-291X(21)00292-8 [pii]
LID - 10.1016/j.bbrc.2021.02.077 [doi]
AB  - PURPOSE: MicroRNAs act as crucial regulators of a diverse range of biological 
      processes, including chemoresistance. Our study aimed to investigate the effect 
      of miR-324-3p on lung adenocarcinoma cell line A549 resistant to 
      cis-diamminedichloroplatinum II (DDP, aka cisplatin). METHODS: The miR-324-3p 
      expression levels in cisplatin-sensitive A549（A549） and cisplatin-resistant A549 
      (A549/DDP) cells were determined by qRT-PCR assay. Cell proliferation was 
      determined with the commercial kit CCK-8 and colony formation assay, whereas cell 
      death was analyzed using flow cytometry. The target gene of miR-324-3p was 
      identified and validated with the luciferase reporter and western blot assays. 
      The role of miR-324-3p in modulating cisplatin resistance was evaluated in vitro. 
      RESULTS: The expression of miR-324-3p was found to be significantly downregulated 
      in the A549/DDP cells. Conversely, miR-324-3p overexpression reversed cisplatin 
      resistance in the cells. With regard to the possible mechanism underlying this 
      phenomenon, we identified the glutathione peroxidase 4 (GPX4) gene as the direct 
      target of miR-324-3p, where overexpression of the gene reversed the miR-324-3p 
      effect of sensitizing the A549/DDP cells to cisplatin. Furthermore, the GPX4 
      inhibitor RSL3 could mimic the effect of miR-324-3p upregulation in increasing 
      the sensitivity of the cisplatin-resistant cells to the drug. Significantly, 
      miR-324-3p enhanced cisplatin-induced ferroptosis in the A549/DDP cells. 
      CONCLUSION: Our findings revealed the role of the miR-324-3p-GPX4 signaling axis 
      in A549/DDP cells and how the targeting of this axis could be a potential 
      strategy for reversing cisplatin resistance in human non small cell lung cancer 
      (NSCLC).
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Deng, Shi-Hua
AU  - Deng SH
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Wu, Dong-Ming
AU  - Wu DM
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Li, Li
AU  - Li L
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Liu, Teng
AU  - Liu T
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Zhang, Ting
AU  - Zhang T
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Li, Jing
AU  - Li J
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Yu, Ye
AU  - Yu Y
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - He, Miao
AU  - He M
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Zhao, Yang-Yang
AU  - Zhao YY
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Han, Rong
AU  - Han R
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China.
FAU - Xu, Ying
AU  - Xu Y
AD  - Clinical Medical College and the First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, Sichuan, 610500, PR China. Electronic address: 
      yingxu825@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210301
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (MIRN324 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - A549 Cells
MH  - Adenocarcinoma of Lung/*genetics/*pathology/ultrastructure
MH  - Base Sequence
MH  - Cisplatin/*pharmacology
MH  - Down-Regulation/drug effects/genetics
MH  - Drug Resistance, Neoplasm/drug effects/*genetics
MH  - Ferroptosis/drug effects/*genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lung Neoplasms/*genetics/pathology/ultrastructure
MH  - MicroRNAs/genetics/*metabolism
MH  - Mitochondria/drug effects/ultrastructure
MH  - Phospholipid Hydroperoxide Glutathione Peroxidase/*metabolism
MH  - Up-Regulation/drug effects/genetics
OTO - NOTNLM
OT  - Cisplatin resistance
OT  - Ferroptosis
OT  - GPX4
OT  - NSCLC
OT  - miR-324-3p
COIS- Declaration of competing interest The authors report no conflicts of interest in 
      this work.
EDAT- 2021/03/05 06:00
MHDA- 2021/09/09 06:00
CRDT- 2021/03/04 20:13
PHST- 2021/02/08 00:00 [received]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/03/05 06:00 [pubmed]
PHST- 2021/09/09 06:00 [medline]
PHST- 2021/03/04 20:13 [entrez]
AID - S0006-291X(21)00292-8 [pii]
AID - 10.1016/j.bbrc.2021.02.077 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Apr 16;549:54-60. doi: 
      10.1016/j.bbrc.2021.02.077. Epub 2021 Mar 1.