Downregulation of miR-1225-5p is pivotal for proliferation, invasion, and migration of HCC cells through NFκB regulation.
NFκB p65
hepatocellular carcinoma
invasion
miR-1225
migration
proliferation
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
11
04
2020
revised:
11
06
2020
accepted:
18
06
2020
pubmed:
29
7
2020
medline:
8
9
2021
entrez:
29
7
2020
Statut:
ppublish
Résumé
As one of the most frequently seen malignancies, hepatocellular carcinoma (HCC) serves as the second largest contributor to malignancy-specific mortality worldwide. MicroRNA-1225-5p (miR-1225) exerts an essential impact on the growth and metastasis of many malignancies. However, the contribution of miR-125 to HCC and the molecular mechanism of cancer cell viability and apoptosis are still unclear. We focused our research on exploring the function and molecular mechanism of miR-1225 in regulating HCC cell growth, migration, and invasion. Quantitative PCR data showed that miR-1225 expression was repressed in HCC cell lines and in the tissues of HCC patients, compared to that in normal human hepatic cells and tissues. Transfection of a miR-1225 mimic inhibited cell viability and proliferation as indicated by CCK-8 staining and MTT assay. Transwell invasion, wound healing assay, and Western blotting were performed to assess whether miR-1225 repressed the metastasis and invasion of HCC cells, and decreased matrix metalloproteinase 9 (MMP9) expression. Further bioinformatic prediction and dual-luciferase reporter assay suggested that miR-1225 targeted the 3'-UTR of NFκB p65. Overexpression of p65 protein counteracted the repressive impact of miR-1225 on invasion, migration, and proliferation of HCC cells. This research provided new evidences that miR-1225 inhibits the viability, migration, and invasion of HCC cells by downregulation of p65.
Sections du résumé
BACKGROUND
BACKGROUND
As one of the most frequently seen malignancies, hepatocellular carcinoma (HCC) serves as the second largest contributor to malignancy-specific mortality worldwide. MicroRNA-1225-5p (miR-1225) exerts an essential impact on the growth and metastasis of many malignancies. However, the contribution of miR-125 to HCC and the molecular mechanism of cancer cell viability and apoptosis are still unclear. We focused our research on exploring the function and molecular mechanism of miR-1225 in regulating HCC cell growth, migration, and invasion.
MATERIAL
METHODS
Quantitative PCR data showed that miR-1225 expression was repressed in HCC cell lines and in the tissues of HCC patients, compared to that in normal human hepatic cells and tissues. Transfection of a miR-1225 mimic inhibited cell viability and proliferation as indicated by CCK-8 staining and MTT assay. Transwell invasion, wound healing assay, and Western blotting were performed to assess whether miR-1225 repressed the metastasis and invasion of HCC cells, and decreased matrix metalloproteinase 9 (MMP9) expression. Further bioinformatic prediction and dual-luciferase reporter assay suggested that miR-1225 targeted the 3'-UTR of NFκB p65.
RESULTS
RESULTS
Overexpression of p65 protein counteracted the repressive impact of miR-1225 on invasion, migration, and proliferation of HCC cells.
CONCLUSION
CONCLUSIONS
This research provided new evidences that miR-1225 inhibits the viability, migration, and invasion of HCC cells by downregulation of p65.
Identifiants
pubmed: 32720731
doi: 10.1002/jcla.23474
pmc: PMC7676203
doi:
Substances chimiques
MIRN1225 microRNA, human
0
MicroRNAs
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23474Informations de copyright
© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.
Références
Clin Cancer Res. 2011 Dec 15;17(24):7539-50
pubmed: 22031094
World J Gastroenterol. 2005 Oct 28;11(40):6258-61
pubmed: 16419152
Biol Chem. 2019 Jan 28;400(2):237-246
pubmed: 30138106
Onco Targets Ther. 2013 Sep 02;6:1167-78
pubmed: 24039437
Pathobiology. 2013;80(3):146-54
pubmed: 23364389
Onco Targets Ther. 2018 Sep 28;11:6339-6350
pubmed: 30319274
J Biol Chem. 1998 Nov 20;273(47):31262-72
pubmed: 9813034
Nat Rev Cancer. 2005 Aug;5(8):591-602
pubmed: 16056258
J Clin Lab Anal. 2020 Nov;34(11):e23474
pubmed: 32720731
Nat Genet. 2002 Aug;31(4):339-46
pubmed: 12149612
PLoS One. 2013 Apr 10;8(4):e61054
pubmed: 23593387
Science. 2003 Jul 18;301(5631):336-8
pubmed: 12869753
Nature. 2004 Sep 16;431(7006):350-5
pubmed: 15372042
J Mammary Gland Biol Neoplasia. 2002 Apr;7(2):177-89
pubmed: 12463738
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
Science. 1998 Sep 11;281(5383):1680-3
pubmed: 9733516
Cell. 2006 Nov 17;127(4):679-95
pubmed: 17110329
Oncotarget. 2016 Jan 26;7(4):4647-63
pubmed: 26684358
Cell Death Dis. 2015 Oct 22;6:e1942
pubmed: 26492375
J Biol Chem. 2000 Mar 3;275(9):6421-7
pubmed: 10692445
FEBS Lett. 1998 Sep 11;435(1):29-34
pubmed: 9755853
Head Neck. 1999 Oct;21(7):627-38
pubmed: 10487950
Nat Rev Cancer. 2003 Jun;3(6):453-8
pubmed: 12778135
J Leukoc Biol. 1995 May;57(5):747-51
pubmed: 7539028
Laryngoscope. 2004 Dec;114(12):2243-8
pubmed: 15564854
Cell Cycle. 2019 May;18(9):990-1000
pubmed: 30990343
Int Rev Cytol. 1993;143:1-62
pubmed: 8449662
Int J Mol Sci. 2015 Oct 16;16(10):24772-90
pubmed: 26501276
Oncogene. 2005 Jan 27;24(5):810-9
pubmed: 15531914
Nat Rev Cancer. 2004 Jan;4(1):71-8
pubmed: 14708027
CA Cancer J Clin. 2007 Jul-Aug;57(4):225-41
pubmed: 17626119
J Pathol. 2016 Jun;239(2):231-41
pubmed: 27174787
Int J Biol Sci. 2014 Mar 21;10(4):415-25
pubmed: 24719559