The miR‐19b‐3p‐MAP2K3‐STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma

Autor: Yelong Chen, Youbin Lin, Xia Yang, Hu Wang, Weiqing Lu, Zhaoyong Liu, Ying Zhang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Cancer Research
Esophageal Neoplasms
MAP Kinase Kinase 3
medicine.disease_cause
STAT3
Mice
0302 clinical medicine
Cell Movement
RC254-282
Research Articles
Feedback
Physiological
Mice
Inbred BALB C
biology
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
General Medicine
Middle Aged
Gene Expression Regulation
Neoplastic
miR‐19b‐3p
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
Mdm2
Female
Esophageal Squamous Cell Carcinoma
Research Article
Adult
STAT3 Transcription Factor
Mice
Nude
03 medical and health sciences
Downregulation and upregulation
MDM2
In vivo
Cell Line
Tumor
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
Protein kinase A
neoplasms
Aged
Cell Proliferation
Cell growth
digestive system diseases
MicroRNAs
030104 developmental biology
MAP2K3
Tumor progression
Case-Control Studies
Cancer research
biology.protein
Carcinogenesis
Zdroj: Molecular Oncology
Molecular Oncology, Vol 15, Iss 5, Pp 1566-1583 (2021)
ISSN: 1878-0261
1574-7891
Popis: 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.
The regulatory function of MAP2K3 was studied in esophageal squamous cell carcinoma (ESCC) progression. MAP2K3 was found to inhibit cell proliferation and invasion via the EGFR–STAT3 signaling pathway. MAP2K3 suppressed STAT3 expression and activation through proteasomal degradation. miR‐19b‐3p could suppress MAP2K3 expression and could be transcriptional activated by STAT3 in ESCC cells.
Databáze: OpenAIRE
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