MiR-200a with CDC7 as a direct target declines cell viability and promotes cell apoptosis in Wilm’s tumor via Wnt/β-catenin signaling pathway
| Autor: | Xiu-Ling Liang, Yu-Long Wang, Pei-Rong Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell Survival Clinical Biochemistry Apoptosis Cell Cycle Proteins Protein Serine-Threonine Kinases Wilms Tumor Flow cytometry 03 medical and health sciences 0302 clinical medicine Cyclin D1 Cell Line Tumor Targeted Molecular Therapy medicine Humans RNA Neoplasm Viability assay Wnt Signaling Pathway Molecular Biology medicine.diagnostic_test Chemistry Wnt signaling pathway Cell Biology General Medicine Kidney Neoplasms Neoplasm Proteins MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Phosphorylation Signal transduction |
| Zdroj: | Molecular and Cellular Biochemistry. 476:2409-2420 |
| ISSN: | 1573-4919 0300-8177 |
| Popis: | MiR-200a acts as a key role in tumor malignant progression. This work purposed to assess the function of miR-200a in Wilm's tumor. Based on bioinformatics analysis, the expression, prognostic value and related pathways of miR-200a and CDC7 (a potential downstream molecule of miR-200a) in Wilm's tumor were analyzed. qRT-PCR was conducted to confirm the miR-200a level in Wilm's tumor cells. The luciferase reporter assay was carried out to verify the binding of miR-200a to 3'-UTR of CDC7. Then, the impacts of miR-200a and CDC7 on cell viability and apoptosis were measured using CCK-8 and flow cytometry assays. Also, western blot was applied to measure the expression of CDC7 as well as Wnt/β-catenin signaling pathway-related proteins and apoptosis proteins. Herein, we revealed that miR-200a was lowly expressed in Wilm's tumor tissues and cells and the low miR-200a expression is closely bound up with death and poor outcomes. Moreover, miR-200a directly targeted and inhibited CDC7 in Wilm's tumor cells. Biological function experiments illustrated that overexpression of miR-200a reduced the viability and elevated the apoptosis of Wilm's tumor cells, while overexpression of CDC7 reversed the inhibitory impact of miR-200a on cell viability and the promoting impact of miR-200a on cell apoptosis. Besides, we revealed that miR-200a/CDC7 axis can decrease the expression of β-Catenin, Cyclin D1 and C-Myc as well as the phosphorylation of GSK-3β, thus inhibiting the Wnt/β-catenin signaling pathway. Furthermore, blocking the Wnt/β-catenin signaling pathway caused an increase on cell apoptosis, while overexpression of CDC7 can reverse these impacts. Collectively, miR-200a/CDC7 axis involved in regulating the malignant phenotype of Wilm's tumor through Wnt/β-catenin signaling pathway, which provides a theoretical basis for targeted molecular therapy of Wilm's tumor. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink