The miR-19b-3p-MAP2K3-STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma.
Adult
Aged
Animals
Case-Control Studies
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Esophageal Neoplasms
/ genetics
Esophageal Squamous Cell Carcinoma
/ genetics
Feedback, Physiological
/ physiology
Female
Gene Expression Regulation, Neoplastic
Humans
MAP Kinase Kinase 3
/ genetics
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Middle Aged
Neoplasm Invasiveness
STAT3 Transcription Factor
/ genetics
MAP2K3
MDM2
STAT3
miR-19b-3p
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
22
01
2021
received:
18
08
2020
accepted:
26
02
2021
pubmed:
5
3
2021
medline:
1
4
2022
entrez:
4
3
2021
Statut:
ppublish
Résumé
Esophageal squamous cell carcinoma (ESCC) is one of the most refractory malignancies worldwide. Mitogen-activated protein kinase 3 (MAP2K3) has a contradictory role in tumor progression, and the function and expression patterns of MAP2K3 in ESCC remain to be determined. We found that MAP2K3 expression to be downregulated in ESCC, and MAP2K3 downregulation correlated with clinically poor survival. MAP2K3 inhibited ESCC cell proliferation and invasion in vitro and in vivo. MAP2K3 suppressed STAT3 expression and activation. Mechanistically, MAPSK3 interacted with MDM2 to promote STAT3 degradation via the ubiquitin-proteasome pathway. Furthermore, exosomal miR-19b-3p derived from the plasma of patients with ESCC could suppress MAP2K3 expression to promote ESCC tumorigenesis. STAT3 was found to bind to the MIR19B promoter and increased the expression of miR-19b-3p in ESCC cells. In summary, our results demonstrated that the miR-19b-3p-MAP2K3-STAT3 feedback loop regulates ESCC tumorigenesis and elucidates the potential of therapeutically targeting this pathway in ESCC.
Identifiants
pubmed: 33660414
doi: 10.1002/1878-0261.12934
pmc: PMC8096789
doi:
Substances chimiques
MIRN19 microRNA, human
0
MicroRNAs
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
MAP Kinase Kinase 3
EC 2.7.12.2
MAP2K3 protein, human
EC 2.7.12.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1566-1583Informations de copyright
© 2021 The Authors. published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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