Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis.
Endometrial cancer
Klf5
Metapristone
Nrf1
miR-492
Journal
Cancer cell international
ISSN: 1475-2867
Titre abrégé: Cancer Cell Int
Pays: England
ID NLM: 101139795
Informations de publication
Date de publication:
07 Jan 2021
07 Jan 2021
Historique:
received:
11
02
2020
accepted:
27
11
2020
entrez:
8
1
2021
pubmed:
9
1
2021
medline:
9
1
2021
Statut:
epublish
Résumé
Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer. RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry. Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo. Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer.
METHODS
METHODS
RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry.
RESULTS
RESULTS
Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo.
CONCLUSION
CONCLUSIONS
Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.
Identifiants
pubmed: 33413440
doi: 10.1186/s12935-020-01682-1
pii: 10.1186/s12935-020-01682-1
pmc: PMC7792070
doi:
Types de publication
Journal Article
Langues
eng
Pagination
29Subventions
Organisme : Natural Science Foundation of Beijing Municipality
ID : 7184211
Organisme : National Natural Science Foundation of China
ID : 81801402
Organisme : Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education
ID : KM201610025023
Références
Nat Cell Biol. 2013 Jun;15(6):546-54
pubmed: 23728460
J BUON. 2012 Oct-Dec;17(4):637-43
pubmed: 23335518
Curr Oncol. 2008 Jun;15(3):126-35
pubmed: 18596890
Cancer Res. 1991 Oct 15;51(20):5632-5
pubmed: 1913680
Obstet Gynecol. 2015 Apr;125(4):1006-1026
pubmed: 25798986
Biomed Pharmacother. 2017 Jun;90:339-349
pubmed: 28376402
Genet Mol Res. 2014 Feb 27;13(1):1288-95
pubmed: 24634186
Annu Rev Cell Dev Biol. 2007;23:175-205
pubmed: 17506695
J Cell Biochem. 2019 Oct;120(10):17593-17601
pubmed: 31140648
Expert Rev Anticancer Ther. 2019 Jan;19(1):51-60
pubmed: 30295094
Front Pharmacol. 2019 Nov 20;10:1296
pubmed: 31824306
Cell Rep. 2019 Dec 24;29(13):4389-4406.e10
pubmed: 31875548
Oncotarget. 2017 Jun 27;8(45):78351-78364
pubmed: 29108234
Med Res Rev. 2014 Sep;34(5):979-1000
pubmed: 24585714
PLoS One. 2015 Aug 07;10(8):e0134969
pubmed: 26252518
J Int Med Res. 2019 Aug;47(8):3803-3817
pubmed: 31187677
Medicine (Baltimore). 2018 Oct;97(43):e12968
pubmed: 30412119
Oncotarget. 2014 May 30;5(10):3246-60
pubmed: 24912774
J Natl Cancer Inst. 2000 Jun 7;92(11):924-30
pubmed: 10841828
Cancer. 2000 Feb 15;88(4):814-24
pubmed: 10679651
Contraception. 2003 Dec;68(6):409-20
pubmed: 14698070
Sci Rep. 2017 Dec 7;7(1):17190
pubmed: 29215040
Obstet Gynecol. 2012 Aug;120(2 Pt 1):383-97
pubmed: 22825101
Liver Int. 2018 Jul;38(7):1280-1291
pubmed: 29314711
Cancer Res. 1991 Oct 1;51(19):5308-14
pubmed: 1913654
Oncotarget. 2015 Nov 3;6(34):35157-72
pubmed: 26459390
Mol Ther Nucleic Acids. 2020 Mar 6;19:61-71
pubmed: 31837606
Gynecol Oncol. 2003 Mar;88(3):263-5
pubmed: 12648572
Biomed Pharmacother. 2017 Jun;90:437-445
pubmed: 28391165
Mol Carcinog. 2018 Jan;57(1):32-43
pubmed: 28802022
Curr Opin Obstet Gynecol. 2019 Feb;31(1):31-37
pubmed: 30571659
Mol Carcinog. 2017 Aug;56(8):1896-1908
pubmed: 28277622
Mol Cell Biochem. 2015 Jul;405(1-2):73-9
pubmed: 25862460
Tumour Biol. 2015 Mar;36(3):1913-21
pubmed: 25407488
Oncogene. 2015 Jul;34(29):3839-47
pubmed: 25284586
Dtsch Arztebl Int. 2010 Aug;108(34-35):571-7
pubmed: 21904591
Int J Cancer. 2019 Feb 1;144(3):582-594
pubmed: 30289973
Cell Mol Life Sci. 2009 Aug;66(16):2691-706
pubmed: 19448973
Curr Top Med Chem. 2015;15(8):699-713
pubmed: 25732792
Oncol Lett. 2019 Oct;18(4):3792-3802
pubmed: 31579409
Cancer Cell Int. 2014 Sep 20;14(1):95
pubmed: 25253996
J Pharm Biomed Anal. 2014 Jul;95:158-63
pubmed: 24682015
IUBMB Life. 2013 Dec;65(12):999-1011
pubmed: 24323942
AAPS J. 2014 Mar;16(2):289-98
pubmed: 24442753
J Clin Endocrinol Metab. 2014 Mar;99(3):871-80
pubmed: 24423290
Cancer Biol Med. 2019 Feb;16(1):55-70
pubmed: 31119046
CA Cancer J Clin. 2017 Jan;67(1):7-30
pubmed: 28055103
Clin Cancer Res. 2004 Aug 1;10(15):5215-25
pubmed: 15297425
Oxid Med Cell Longev. 2019 Sep 4;2019:2647068
pubmed: 31687076
Lancet. 2005 Aug 6-12;366(9484):491-505
pubmed: 16084259