Demethylated miR-216a Regulates High Mobility Group Box 3 Promoting Growth of Esophageal Cancer Cells Through Wnt/β-Catenin Pathway
Autor: | Lei Qi, Cheng-Xi Sun, Feng Zhu |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Reporter gene DNA methylation HMGB3 Chemistry Cell growth Wnt signaling pathway Methylation lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens lcsh:RC254-282 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Real-time polymerase chain reaction Oncology miR-216a 030220 oncology & carcinogenesis Catenin microRNA Cancer research Wnt/β-catenin pathway esophageal cancer Original Research |
Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 11 (2021) |
ISSN: | 2234-943X |
DOI: | 10.3389/fonc.2021.622073 |
Popis: | BackgroundEsophageal cancer (EC) is the eighth most common cause of cancer-associated mortality in humans. Recent studies have revealed the important roles of microRNAs (miRs) in mediating tumor initiation and progression. miR-216a has been found to be involved in the progression of EC, but the underlying mechanisms remain largely unknown. The aim of this study is to explore the mechanism of miR-216a and the downstream molecules in esophageal cancer.Materials and MethodsThe degree of methylation of miR-216a promoter in EC tissues and cell lines was determined with methylation specific polymerase chain reaction (MSP). The levels of miR-216a and HMGB3 in EC cells were quantified by quantitative PCR (qPCR) and Western blot (WB). EC cell lines were treated with DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-AZ), miR-216a mimics, and HMGB3 siRNA to explore the effects of miR-216a and HMGB3 on the proliferation, migration, invasion, and apoptosis of cells. Dual-luciferase reporter assay was employed to verify the binding of miR-216a to the 3’UTR of HMGB2 mRNA.ResultsThe promoter of MiR-216a was hypermethylated and the expression of miR-216a was down-regulated in EC, while HMGB3 was up-regulated. Dual luciferase reporter assay confirmed the binding of miR-216a to the 3’UTR of HMGB3 mRNA. Demethylated miR-216a and miR-216a mimics elevated miR-216a expression and down-regulated HMGB3, as well as inhibited cell proliferation, migration, and invasion. Inhibiting the expression of HMGB3 played an important role in inducing apoptosis, suppressing cell expansion, and down-regulating the activity of Wnt/β-catenin pathway.ConclusionsHypermethylation in the promoter of miR-216a upregulated HMGB3 and the Wnt/β-catenin pathway, resulting in enhanced EC progression. |
Databáze: | OpenAIRE |
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