MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways

Autor: Jingwen Ma, Jun Wei, Liwei Yuan, Linlin Wang, Yani Huang, Zhijuan Yang, Shiyun Zhao, Dan Liu
Rok vydání: 2021
Předmět:
0301 basic medicine
MAPK/ERK pathway
Cancer Research
Epithelial-Mesenchymal Transition
Stromal cell
Apoptosis
Pathology and Forensic Medicine
MAPK1
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
miRNA-543
Cell Movement
Endometrial Stromal Tumors
Transforming Growth Factor beta
endometrial stromal cell
Biomarkers
Tumor

Tumor Cells
Cultured

Humans
molecular biology
Epithelial–mesenchymal transition
Protein kinase A
beta Catenin
Cell Proliferation
Original Research
Endometrial Stromal Cell
Chemistry
Wnt signaling pathway
General Medicine
Endometrial Neoplasms
Cell biology
Gene Expression Regulation
Neoplastic

Wnt Proteins
MicroRNAs
Society Journal Archive
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
embryonic structures
Female
Mitogen-Activated Protein Kinases
Signal transduction
wnt/β-catenin
Zdroj: Pathology and Oncology Research
ISSN: 1532-2807
Popis: Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3′ untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.
Databáze: OpenAIRE