FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance.
Journal
Analytical cellular pathology (Amsterdam)
ISSN: 2210-7185
Titre abrégé: Anal Cell Pathol (Amst)
Pays: United States
ID NLM: 101541993
Informations de publication
Date de publication:
2022
2022
Historique:
received:
08
02
2022
accepted:
26
03
2022
entrez:
2
5
2022
pubmed:
3
5
2022
medline:
4
5
2022
Statut:
epublish
Résumé
Cervical cancer (CC) is among the most prevalent cancers among female populations with high recurrence rates all over the world. Cisplatin (DDP) is the first-line treatment for multiple cancers, including CC. The main problem associated with its clinical application is drug resistance. This study is aimed at investigating the function and downstream regulation mechanism of forkhead-box A1 (FOXA1) in CC, which was verified as an oncogene in several cancers. Using GEO database and bioinformatics analysis, we identified FOXA1 as a possible oncogene in CC. Silencing of FOXA1 inhibited CC cell growth, invasion, and chemoresistance. Afterwards, the downstream gene of FOXA1 was predicted using a bioinformatics website and validated using ChIP and dual-luciferase assays. SIX4, a possible target of FOXA1, promoted CC cell malignant aggressiveness and chemoresistance. In addition, overexpression of SIX4 promoted phosphorylation of PI3K and AKT proteins and activated the PI3K/AKT signaling pathway. Further overexpression of SIX4 reversed the repressive effects of FOXA1 knockdown on CC cell growth, invasion, and chemoresistance in DDP-resistant cells. FOXA1-induced SIX4 facilitates CC progression and chemoresistance, highlighting a strong potential for FOXA1 to serve as a promising therapeutic target in CC.
Identifiants
pubmed: 35498155
doi: 10.1155/2022/9675466
pmc: PMC9045987
doi:
Substances chimiques
FOXA1 protein, human
0
Hepatocyte Nuclear Factor 3-alpha
0
Homeodomain Proteins
0
SIX4 protein, human
0
Trans-Activators
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9675466Informations de copyright
Copyright © 2022 Zhuo Wang et al.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
EBioMedicine. 2019 Jun;44:150-161
pubmed: 31147293
Cancer Lett. 2020 Dec 28;495:200-210
pubmed: 32931885
Thorac Cancer. 2021 Mar;12(6):752-759
pubmed: 33481352
Tumori. 2016 Jun 2;2016(3):236-43
pubmed: 27056337
CA Cancer J Clin. 2021 Jan;71(1):7-33
pubmed: 33433946
Oncogene. 2020 Dec;39(50):7279-7295
pubmed: 33046796
Mol Cancer. 2021 May 18;20(1):77
pubmed: 34006303
Am J Cancer Res. 2020 Jan 01;10(1):224-236
pubmed: 32064163
Cancer Cell Int. 2020 Aug 12;20:389
pubmed: 32831649
Drug Des Devel Ther. 2016 Jun 07;10:1885-95
pubmed: 27354763
J Int Med Res. 2020 Dec;48(12):300060520971453
pubmed: 33296605
Proc Natl Acad Sci U S A. 2019 Dec 11;:
pubmed: 31826955
Cold Spring Harb Perspect Med. 2018 Nov 1;8(11):
pubmed: 29530947
Biochem Biophys Res Commun. 2019 Aug 27;516(3):851-857
pubmed: 31266633
Neoplasia. 2020 Aug;22(8):294-310
pubmed: 32512502
Cancer Sci. 2014 Nov;105(11):1377-83
pubmed: 25155268
Lancet. 2019 Jan 12;393(10167):169-182
pubmed: 30638582
Exp Cell Res. 2020 Sep 15;394(2):112141
pubmed: 32535033
Exp Mol Pathol. 2017 Apr;102(2):230-236
pubmed: 28209524
Cell Death Dis. 2017 Oct 26;8(10):e3143
pubmed: 29072684
Cell Biochem Funct. 2020 Jan;38(1):66-76
pubmed: 31702057
J Hematol Oncol. 2016 Nov 8;9(1):119
pubmed: 27821176
Breast Cancer Res Treat. 2021 Apr;186(2):317-326
pubmed: 33417085
Int J Oncol. 2014 Sep;45(3):1232-40
pubmed: 24970368
Pharmazie. 2016 Dec 1;71(12):715-718
pubmed: 29442000
J Clin Invest. 2021 Jul 15;131(14):
pubmed: 34101624
Neoplasma. 2019 Mar 5;66(2):211-221
pubmed: 30509104
Pharmacol Rev. 2012 Jul;64(3):706-21
pubmed: 22659329
Mol Carcinog. 2021 Jun;60(6):365-376
pubmed: 33819358
PeerJ. 2017 May 30;5:e3394
pubmed: 28584719
Bioorg Chem. 2019 Jul;88:102925
pubmed: 31003078
Gut. 2021 May;70(5):900-914
pubmed: 32826305
Cancers (Basel). 2021 Mar 09;13(5):
pubmed: 33803151