Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt/β-catenin-TFE3 feedback loop signalling.
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/ genetics
Cell Death
Cell Proliferation
/ genetics
Cell Transformation, Neoplastic
/ genetics
Colonic Neoplasms
/ genetics
Feedback
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Iron
/ metabolism
MicroRNAs
/ genetics
RNA, Long Noncoding
/ genetics
Stearoyl-CoA Desaturase
/ genetics
beta Catenin
/ genetics
LINC01606
SCD1
Wnt/β-catenin
colon cancer
ferroptosis
lipid peroxidation
Journal
Clinical and translational medicine
ISSN: 2001-1326
Titre abrégé: Clin Transl Med
Pays: United States
ID NLM: 101597971
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
12
02
2022
received:
14
10
2021
accepted:
15
02
2022
pubmed:
30
4
2022
medline:
3
5
2022
entrez:
29
4
2022
Statut:
ppublish
Résumé
Ferroptosis is principally caused by iron catalytic activity and intracellular lipid peroxidation. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the potential interplay between lncRNA LINC01606 and ferroptosis in colon cancer remains elusive. The expression level of LNC01606 in colon cancer tissue was detected by quantitative real-time polymerase chain reaction. The functional role of LNC01606 was investigated by gain- and loss-of-function assays both in vitro and in vivo. The LINC01606-SCD1-Wnt/β-catenin-TFE3 axis were screened and validated by DNA/RNA pull down, gas chromatography-mass spectrometry, RNA immunoprecipitation and dual-luciferase reporter. The expression of lncRNA LINC01606 was frequently upregulated in human colon cancer and strongly associated with a poor prognosis. LINC01606 functioned as an oncogene and promotes colon cancer cell growth, invasion and stemness both in vitro and in vivo. Moreover, LINC01606 protected colon cancer cells from ferroptosis by decreasing the concentration of iron, lipid reactive oxygen species, mitochondrial superoxide and increasing mitochondrial membrane potential. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/β-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. Furthermore, we confirmed that upregulated LINC01606 and Wnt/β-catenin formed a positive feedback regulatory loop, further inhibiting ferroptosis and enhancing stemness. LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer.
Sections du résumé
BACKGROUND
Ferroptosis is principally caused by iron catalytic activity and intracellular lipid peroxidation. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the potential interplay between lncRNA LINC01606 and ferroptosis in colon cancer remains elusive.
METHODS
The expression level of LNC01606 in colon cancer tissue was detected by quantitative real-time polymerase chain reaction. The functional role of LNC01606 was investigated by gain- and loss-of-function assays both in vitro and in vivo. The LINC01606-SCD1-Wnt/β-catenin-TFE3 axis were screened and validated by DNA/RNA pull down, gas chromatography-mass spectrometry, RNA immunoprecipitation and dual-luciferase reporter.
RESULTS
The expression of lncRNA LINC01606 was frequently upregulated in human colon cancer and strongly associated with a poor prognosis. LINC01606 functioned as an oncogene and promotes colon cancer cell growth, invasion and stemness both in vitro and in vivo. Moreover, LINC01606 protected colon cancer cells from ferroptosis by decreasing the concentration of iron, lipid reactive oxygen species, mitochondrial superoxide and increasing mitochondrial membrane potential. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/β-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. Furthermore, we confirmed that upregulated LINC01606 and Wnt/β-catenin formed a positive feedback regulatory loop, further inhibiting ferroptosis and enhancing stemness.
CONCLUSIONS
LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer.
Identifiants
pubmed: 35485210
doi: 10.1002/ctm2.752
pmc: PMC9052012
doi:
Substances chimiques
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
0
MicroRNAs
0
RNA, Long Noncoding
0
TFE3 protein, human
0
beta Catenin
0
Iron
E1UOL152H7
SCD1 protein, human
EC 1.14.19.1
Stearoyl-CoA Desaturase
EC 1.14.19.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e752Informations de copyright
© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
Références
Oncol Rep. 2021 Jan;45(1):29-48
pubmed: 33155665
Cancer Res. 2019 Oct 15;79(20):5355-5366
pubmed: 31270077
Prostaglandins Leukot Essent Fatty Acids. 2013 Sep;89(4):203-13
pubmed: 23932824
Cell Rep. 2020 Dec 1;33(9):108444
pubmed: 33264619
Cancer Res. 2018 Jul 1;78(13):3484-3496
pubmed: 29588351
Nucleic Acids Res. 2014 Jan;42(Database issue):D92-7
pubmed: 24297251
Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):E4966-75
pubmed: 27506793
Nat Rev Clin Oncol. 2021 May;18(5):280-296
pubmed: 33514910
Cell Rep. 2020 Dec 8;33(10):108487
pubmed: 33296645
Nat Genet. 2015 Mar;47(3):199-208
pubmed: 25599403
Signal Transduct Target Ther. 2020 Jun 30;5(1):108
pubmed: 32606298
Aging (Albany NY). 2020 Jul 29;12(15):15374-15391
pubmed: 32726752
Commun Biol. 2020 Aug 17;3(1):450
pubmed: 32807853
Front Oncol. 2021 Mar 02;11:619242
pubmed: 33738257
Nat Struct Mol Biol. 2015 Jan;22(1):5-7
pubmed: 25565026
Redox Biol. 2021 Jul;43:102006
pubmed: 34030117
Eur J Pharm Sci. 2020 Sep 1;152:105450
pubmed: 32621966
Int J Biochem Cell Biol. 2018 Oct;103:125-134
pubmed: 30142387
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
Cell Rep. 2017 Feb 28;18(9):2256-2268
pubmed: 28249169
Life Sci. 2020 Nov 1;260:118305
pubmed: 32827544
EMBO J. 2002 Jun 3;21(11):2703-14
pubmed: 12032083
Cell Death Differ. 2016 Jul;23(7):1099-109
pubmed: 26967968
Int J Mol Sci. 2019 Jun 03;20(11):
pubmed: 31163602
Mol Cell. 2022 Feb 17;82(4):728-740
pubmed: 34965379
Hum Mol Genet. 2019 Oct 1;28(19):3270-3281
pubmed: 31272105
Sci Rep. 2019 Nov 7;9(1):16185
pubmed: 31700067
Nucleic Acids Res. 2018 Jan 4;46(D1):D794-D801
pubmed: 29126249
Nat Rev Mol Cell Biol. 2021 Apr;22(4):266-282
pubmed: 33495651
Mol Ther. 2021 Jan 6;29(1):263-274
pubmed: 33002417
Environ Toxicol. 2021 Apr;36(4):520-529
pubmed: 33166055
Mol Cancer. 2019 Mar 30;18(1):66
pubmed: 30927915
Biotechnol Adv. 2018 Nov 1;36(6):1724-1729
pubmed: 29447918
Mol Pharm. 2019 Jun 3;16(6):2532-2539
pubmed: 31009228
Sci Signal. 2014 Jan 21;7(309):ra9
pubmed: 24448649
Oxid Med Cell Longev. 2021 Apr 1;2021:6629804
pubmed: 33868572
Nucleic Acids Res. 2020 Jan 8;48(D1):D863-D870
pubmed: 31701128
Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):358-65
pubmed: 16778563
Front Oncol. 2021 May 11;11:654076
pubmed: 34046350
J Biomed Nanotechnol. 2020 Nov 1;16(11):1612-1622
pubmed: 33461653
Oncogene. 2018 May;37(18):2367-2378
pubmed: 29445137
Nat Struct Mol Biol. 2015 Jul;22(7):581-5
pubmed: 26098317
Aging (Albany NY). 2020 May 26;12(10):9085-9102
pubmed: 32453709
Cell. 2017 Oct 5;171(2):273-285
pubmed: 28985560
Nat Med. 2015 Nov;21(11):1253-61
pubmed: 26540387
Cell Stem Cell. 2017 Mar 2;20(3):303-314.e5
pubmed: 28041894
Pharmacol Res. 2015 Sep;99:36-43
pubmed: 26003288
Cell Rep. 2012 Nov 29;2(5):1316-28
pubmed: 23122960
Nat Chem Biol. 2017 Jan;13(1):81-90
pubmed: 27842066
Cell Death Dis. 2020 Sep 14;11(9):751
pubmed: 32929075
ACS Chem Biol. 2018 Apr 20;13(4):1013-1020
pubmed: 29512999
Clin Transl Med. 2022 Apr;12(4):e752
pubmed: 35485210
IUBMB Life. 2017 Jun;69(6):423-434
pubmed: 28276141
Cell Death Differ. 2019 Nov;26(11):2329-2343
pubmed: 30787392
Nucleic Acids Res. 2022 Jan 7;50(D1):D165-D173
pubmed: 34850907
Cell. 2012 May 25;149(5):1060-72
pubmed: 22632970