The HOXC-AS2/miR-876-5p/HKDC1 axis regulates endometrial cancer progression in a high glucose-related tumor microenvironment.
HKDC1
endometrial cancer
high glucose
pyroptosis
tumor microenvironment
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
revised:
22
04
2022
received:
12
12
2021
accepted:
25
04
2022
pubmed:
30
4
2022
medline:
15
7
2022
entrez:
29
4
2022
Statut:
ppublish
Résumé
The tumor microenvironment (TME) is related to chronic inflammation and is currently identified as a risk factor for the occurrence and development of endometrial cancer (EC). Pyroptosis is a new proinflammatory form of programmed cell death that plays a critical role in the progression of multiple diseases. However, the important role of pyroptosis in high-glucose (HG)-related EC and the underlying molecular mechanisms remain elusive. In the present study, transcriptome high-throughput sequencing revealed significantly higher hexokinase domain-containing 1 (HKDC1) expression in EC patients with diabetes than in EC patients with normal glucose. Mechanistically, HKDC1 regulates HG-induced cell pyroptosis by modulating the production of reactive oxygen species and pyroptosis-induced cytokine release in EC. In addition, HKDC1 regulates TME formation by enhancing glycolysis, promoting a metabolic advantage in lactate-rich environments to further accelerate EC progression. Subsequently, miR-876-5p was predicted to target the HKDC1 mRNA, and HOXC-AS2 was identified to potentially inhibit the miR-876-5p/HKDC1 axis in regulating cell pyroptosis in HG-related EC. Collectively, we elucidated the regulatory role of the HOXC-AS2/miR-876-5p/HKDC1 signal transduction axis in EC cell pyroptosis at the molecular level, which may provide an effective therapeutic target for patients with diabetes who are diagnosed with EC.
Identifiants
pubmed: 35485648
doi: 10.1111/cas.15384
pmc: PMC9277262
doi:
Substances chimiques
MIRN876 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
HKDC1 protein, human
EC 2.7.1.1
Hexokinase
EC 2.7.1.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2297-2310Subventions
Organisme : Taishan Scholars
ID : ts201511073
Organisme : Shenzhen Healthcare Research Project
ID : SZLY2017030
Organisme : Special Fund for Scientific Talents of the First Affiliated Hospital of Xiamen University
ID : ZLYY201906
Organisme : Sanming Project of Medicine in Shenzhen
ID : SZSM201812075
Organisme : Xiamen Medical and Health Guiding Project Fund Project
ID : 3502Z20214ZD1020
Organisme : National Natural Science Foundation of China
ID : NSFC81672591
Organisme : National Major Scientific and Technological Special Project for "Significant New Drugs Development"
ID : 2020ZX09201005
Organisme : Fujian Natural Science Foundation (Youth Innovation) Project
ID : 2020J05308
Informations de copyright
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Cancer Res. 2019 Sep 15;79(18):4557-4566
pubmed: 31350295
Int J Mol Sci. 2019 Nov 16;20(22):
pubmed: 31744051
J Cell Mol Med. 2020 Apr;24(8):4533-4546
pubmed: 32150330
Endocrinology. 2019 Feb 1;160(2):313-330
pubmed: 30517626
J Agric Food Chem. 2020 Feb 5;68(5):1326-1336
pubmed: 31955565
Trends Genet. 2016 Apr;32(4):211-224
pubmed: 26922301
J Mol Cell Biol. 2019 Dec 19;11(12):1069-1082
pubmed: 30860577
Trends Neurosci. 2020 Jan;43(1):55-73
pubmed: 31843293
EMBO Rep. 2019 Jun;20(6):
pubmed: 31101676
Exp Cell Res. 2020 Apr 1;389(1):111880
pubmed: 32017930
BMC Cancer. 2019 May 31;19(1):527
pubmed: 31151429
Cancer Sci. 2022 Jul;113(7):2297-2310
pubmed: 35485648
J Exp Clin Cancer Res. 2020 Jan 13;39(1):9
pubmed: 31928530
Cell Death Dis. 2019 Sep 9;10(9):650
pubmed: 31501419
Immunol Rev. 2017 May;277(1):61-75
pubmed: 28462526
Biomed Pharmacother. 2019 Nov;119:109396
pubmed: 31505425
Biomed Pharmacother. 2020 May;125:109839
pubmed: 32006897
Int J Mol Sci. 2019 Jun 29;20(13):
pubmed: 31261963
Int J Mol Sci. 2020 Dec 16;21(24):
pubmed: 33339180
Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10410-10418
pubmed: 33155197
Gynecol Oncol. 2015 Sep;138(3):668-75
pubmed: 26135947
Cancer Cell Int. 2020 Sep 12;20:450
pubmed: 32943998
BMC Cancer. 2019 Nov 21;19(1):1130
pubmed: 31752758
Anticancer Res. 2018 Jul;38(7):4169-4178
pubmed: 29970546
Cancer Sci. 2021 Oct;112(10):3979-3994
pubmed: 34252266
Front Immunol. 2018 Dec 11;9:2918
pubmed: 30619282
Am J Transl Res. 2020 Aug 15;12(8):4422-4433
pubmed: 32913516
Front Immunol. 2020 Jul 17;11:1402
pubmed: 32765498
Trends Biochem Sci. 2016 Dec;41(12):1012-1021
pubmed: 27669650
Arch Gynecol Obstet. 2016 Jun;293(6):1287-95
pubmed: 26437953
J Transl Med. 2020 Feb 18;18(1):92
pubmed: 32070368
Nat Rev Microbiol. 2009 Feb;7(2):99-109
pubmed: 19148178
Nat Commun. 2019 Mar 4;10(1):1034
pubmed: 30833558
Trends Biochem Sci. 2017 Apr;42(4):245-254
pubmed: 27932073
Biomaterials. 2020 Oct;255:120187
pubmed: 32590192
Onco Targets Ther. 2019 Sep 16;12:7601-7609
pubmed: 31571911
Front Oncol. 2019 Apr 17;9:290
pubmed: 31058090
Life Sci. 2020 Jan 1;240:117138
pubmed: 31809715
BMC Cancer. 2020 Jan 10;20(1):28
pubmed: 31924176
Asian Pac J Cancer Prev. 2018 May 26;19(5):1295-1302
pubmed: 29802690
J Clin Oncol. 2016 Dec 10;34(35):4225-4230
pubmed: 27903150
Endocrinology. 2016 Sep;157(9):3452-61
pubmed: 27459389
Mol Cancer Res. 2019 Jun;17(6):1316-1325
pubmed: 30796177
Biomed Pharmacother. 2020 Jan;121:109595
pubmed: 31710896
Immunol Rev. 2011 Sep;243(1):206-14
pubmed: 21884178
Int Immunopharmacol. 2019 Feb;67:458-464
pubmed: 30594776
Biochem Biophys Res Commun. 2021 Jun 18;558:147-153
pubmed: 33915328
Int Immunopharmacol. 2019 Feb;67:311-318
pubmed: 30572256
Trends Mol Med. 2007 Jun;13(6):252-9
pubmed: 17452018
PLoS One. 2013 Nov 06;8(11):e77955
pubmed: 24223129