miR-498 inhibits autophagy and M2-like polarization of tumor-associated macrophages in esophageal cancer via MDM2/ATF3
| Autor: | Shishan Deng, Dezhi Li, Lina Tang, Sijia Yu, Xingsheng Hu, Fengfei Sun, Junmei Song, Min Yan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Esophageal Neoplasms Macrophage polarization Inflammation Biology Models Biological Mice Cell Line Tumor Tumor-Associated Macrophages microRNA Autophagy Tumor Microenvironment Genetics medicine Animals Humans Macrophage Activating Transcription Factor 3 Gene Expression Profiling Computational Biology Proto-Oncogene Proteins c-mdm2 Macrophage Activation Esophageal cancer Prognosis medicine.disease Phenotype Gene Expression Regulation Neoplastic Disease Models Animal MicroRNAs Cancer research biology.protein Mdm2 Female RNA Interference Disease Susceptibility medicine.symptom Biomarkers |
| Zdroj: | Epigenomics. 13:1013-1030 |
| ISSN: | 1750-192X 1750-1911 |
| DOI: | 10.2217/epi-2020-0341 |
| Popis: | Structured abstractLay abstract In this study, we aimed to elucidate the therapeutic mechanism of miRNA (miR)-498 in autophagy and macrophage polarization to M2-like phenotype in esophageal cancer. This study reports lower miR-498 expression in esophageal cancer tissues compared with adjacent normal tissues. According to the experimental results, miR-498 negatively targets MDM2 by binding to its 3′UTR, which leads to attenuated ubiquitination and degradation of ATF3 induced by MDM2. Specifically, overexpressed miR-498 reduces ratio of LC3II (a marker that is commonly utilized to detect cell autophagy) to LC3I and increases p62 (a common cargo receptor for autophagy) accumulation in KYSE-150 cells, and elevates macrophage polarization to M2-like phenotype by depressing MDM2-mediated ATF3 degradation. The present study deepened our understanding of the causes of esophageal cancer and provided at least three novel therapeutic targets for the development of effective targeted therapy for esophageal cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|