microR-4449 Promotes Colorectal Cancer Cell Proliferation via Regulation of SOCS3 and Activation of STAT3 Signaling.
SOCS3
STAT3
colorectal cancer
microR-4449
Journal
Cancer management and research
ISSN: 1179-1322
Titre abrégé: Cancer Manag Res
Pays: New Zealand
ID NLM: 101512700
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
06
2020
accepted:
21
10
2020
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
16
4
2021
Statut:
epublish
Résumé
Dysregulation of microRNAs (miRNAs), which represented a critical level of gene expression modulation, regulated the development of colorectal cancer. However, the functions of numerous miRNAs remain unclear in colorectal cancer. The microarray data of GSE115513 were retrieved; subsequently, the differentially expressed miRNAs between 411 colon tumors and 381 normal colon mucosa were analyzed. Real-time PCR (RT-qPCR) and bioinformatic analysis were applied to examine the expression of miR-4449 in collected colorectal tumors and published microarray data. The activity of signal transducer and activator of transcription 3 (STAT3) signaling was detected by Western blotting and RT-qPCR. Dual-Luciferase assay and bioinformatic analysis were used to confirm the interaction between suppressor of cytokine signaling 3 (SOCS3) and miR-4449. Loss of function and rescue assays were performed to study the involvement of miR-4449 and SOCS3 in cell proliferation and apoptosis of colorectal cancer. Herein, we identified miR-4449 as a novel upregulated miRNA in colorectal cancer. Our data suggested that miR-4449 downregulation blocked the proliferation of colorectal cancer cells accompanied with the elevation of cell apoptosis. Decreased expression of miR-4449 led to inactivation of STAT3 pathway as indicated by dephosphorylation of STAT3 and downregulation of STAT3 target genes, including vascular endothelial growth factor (VEGF), c-Myc, baculovirus inhibitor of apoptosis containing 5 (BIRC5). Furthermore, SOCS3, a negative regulator of STAT3 pathway, was found to be a target gene of miR-4449. The data also showed that the inactivation of STAT3 pathway by miR-4449 inhibitor was realized by targeting SOCS3. Moreover, the biological function of miR-4449 downregulation was reversed by SOCS3 knockdown in colorectal cancer cells. The current study revealed that miR-4449 promoted cell proliferation of colorectal cancer and was a promising potential therapeutic target for colorectal cancer.
Identifiants
pubmed: 33854373
doi: 10.2147/CMAR.S266153
pii: 266153
pmc: PMC8039016
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3029-3039Informations de copyright
© 2021 Yan et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests in this work.
Références
J Clin Lab Anal. 2019 Nov;33(9):e23003
pubmed: 31541491
Front Oncol. 2019 Feb 19;9:76
pubmed: 30838175
J Hematol Oncol. 2013 Dec 05;6:90
pubmed: 24308725
Anticancer Res. 2016 Mar;36(3):1093-102
pubmed: 26977004
Nat Immunol. 2003 Jun;4(6):540-5
pubmed: 12754505
Semin Liver Dis. 2015 Feb;35(1):3-11
pubmed: 25632930
J Cancer. 2018 Oct 6;9(21):3867-3873
pubmed: 30410589
Clin Chem Lab Med. 2017 May 1;55(5):748-754
pubmed: 27155004
World J Gastroenterol. 2012 Aug 7;18(29):3839-48
pubmed: 22876036
Cell Death Dis. 2018 Jan 18;9(2):25
pubmed: 29348540
Eur Rev Med Pharmacol Sci. 2017 Nov;21(22):5153-5159
pubmed: 29228427
Cancer Med. 2017 Jun;6(6):1331-1340
pubmed: 28440035
Cell Death Dis. 2018 Jan 9;9(1):11
pubmed: 29317607
Oncotarget. 2017 Jul 25;8(30):49807-49823
pubmed: 28591704
Cell Death Dis. 2019 Feb 20;10(3):175
pubmed: 30787278
Science. 1994 Apr 1;264(5155):95-8
pubmed: 8140422
Acta Biochim Pol. 2012;59(4):467-74
pubmed: 23173124
Nature. 2014 Jan 16;505(7483):344-52
pubmed: 24429633
Gut. 2010 Feb;59(2):227-35
pubmed: 19926618
Gene. 2017 Sep 5;627:114-122
pubmed: 28603075
JAKSTAT. 2013 Jul 1;2(3):e24053
pubmed: 24069550
Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1487-1493
pubmed: 30840270
Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4227-32
pubmed: 10760290
Mol Ther. 2018 Mar 7;26(3):744-754
pubmed: 29475734
J Cancer. 2020 Mar 26;11(12):3634-3644
pubmed: 32284760
Oncol Rep. 2017 Jun;37(6):3227-3234
pubmed: 28498395
PLoS One. 2013 Aug 05;8(8):e70300
pubmed: 23940556
Nat Rev Genet. 2010 Sep;11(9):597-610
pubmed: 20661255
Nat Commun. 2019 Jul 10;10(1):3039
pubmed: 31292446
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Cancer Cell Int. 2019 Mar 14;19:57
pubmed: 30918473
J Biomed Sci. 2018 Aug 2;25(1):60
pubmed: 30068339
Cell Oncol (Dordr). 2020 Jun;43(3):461-475
pubmed: 32207044
Carcinogenesis. 2016 Mar;37(3):245-261
pubmed: 26740022
Onco Targets Ther. 2019 Dec 10;12:10799-10809
pubmed: 31849487
BMC Cancer. 2017 Nov 7;17(1):723
pubmed: 29115941
Cell Oncol (Dordr). 2019 Dec;42(6):757-768
pubmed: 31359293
PLoS One. 2016 Aug 09;11(8):e0160125
pubmed: 27504822
Int J Oncol. 2014 Apr;44(4):1032-40
pubmed: 24430672
Nat Rev Immunol. 2007 Jun;7(6):454-65
pubmed: 17525754
World J Gastroenterol. 2015 Feb 14;21(6):1804-13
pubmed: 25684945