MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2
| Autor: | Xiaohua Lv, Yu-Zhen Zhu, Jue Ning, Yun Tu, Feng Yan Yu, Ying Deng, Cancan Guo, Hua Ye |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer Bisulfite sequencing Down-Regulation Mice Nude Motility Biology Bioinformatics Epigenesis Genetic law.invention Mice 03 medical and health sciences 0302 clinical medicine HMGA2 law medicine Animals Humans Genes Tumor Suppressor Cell Proliferation Pharmacology Cell growth HMGA2 Protein Methylation DNA Methylation HCT116 Cells Prognosis medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology CpG site 030220 oncology & carcinogenesis biology.protein Cancer research Heterografts Molecular Medicine Suppressor Colorectal Neoplasms Research Paper |
| Zdroj: | Cancer Biology & Therapy. 17:1149-1157 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.1080/15384047.2016.1235661 |
| Popis: | This study aimed to understand the exact function and potential mechanism of miR-4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was decreased in both CRC cells and tissues, and downregulated miR-4500 indicated advanced tumor stage and poor survival. By bisulfite sequencing analysis, we found that the CpG island in the promoter region of miR-4500 was hypermethylated in CRC cells and tissues compared with normal control cells and non-tumor tissues, respectively. Functionally, gain- and loss-of-function analyses indicated the tumor suppressor role of miR-4500: it suppressed cell proliferation, cell cycle progression, migration, and invasion. Predictive algorithms and experimental analyses identified HMGA2 as a direct target of miR-4500. Reintroducing HMGA2 impaired the inhibitory effects of miR-4500 on cell growth and motility. Clinically, higher HMGA2 protein expression in CRC tissues was associated with advanced tumor stage and poor survival. An inverse correlation was found between miR-4500 levels and HMGA2 protein expression. Taken together, this study provides the first evidence that miR-4500 functions as a novel tumor suppressor in the miR-4500/HMGA2 axis in colorectal carcinogenesis, and restoring miR-4500 expression might represent a promising therapeutic strategy for CRC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|