| RRC ID |
57870
|
| 著者 |
Gailhouste L, Liew LC, Yasukawa K, Hatada I, Tanaka Y, Kato T, Nakagama H, Ochiya T.
|
| タイトル |
MEG3-derived miR-493-5p overcomes the oncogenic feature of IGF2-miR-483 loss of imprinting in hepatic cancer cells.
|
| ジャーナル |
Cell Death Dis
|
| Abstract |
Numerous studies have described the critical role played by microRNAs (miRNAs) in cancer progression and the potential of these small non-coding RNAs for diagnostic or therapeutic applications. However, the mechanisms responsible for the altered expression of miRNAs in malignant cells remain poorly understood. Herein, via epigenetic unmasking, we identified a group of miRNAs located in the imprinted delta like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3 (MEG3) locus that were repressed in hepatic tumor cells. Notably, miR-493-5p epigenetic silencing was correlated with hypermethylation of the MEG3 differentially regulated region (DMR) in liver cancer cell lines and tumor tissues from patients. Experimental rescue of miR-493-5p promoted an anti-cancer response by hindering hepatocellular carcinoma (HCC) cell growth in vitro and tumor progression in vivo. We found that miR-493-5p mediated part of its tumor-suppressor activity by abrogating overexpression of insulin-like growth factor 2 (IGF2) and the IGF2-derived intronic oncomir miR-483-3p in HCC cells characterized by IGF2 loss of imprinting (LOI). In summary, this study describes an unknown miRNA-dependent regulatory mechanism between two distinct imprinted loci and a possible therapeutic window for liver cancer patients exhibiting IGF2-miR-483 LOI and amplification.
|
| 巻・号 |
10(8)
|
| ページ |
553
|
| 公開日 |
2019-7-18
|
| DOI |
10.1038/s41419-019-1788-6
|
| PII |
10.1038/s41419-019-1788-6
|
| PMID |
31320614
|
| PMC |
PMC6639415
|
| MeSH |
Animals
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement / genetics
Cell Survival / genetics
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic / genetics
Genes, Tumor Suppressor
Genomic Imprinting / genetics*
Humans
Insulin-Like Growth Factor II / genetics*
Insulin-Like Growth Factor II / metabolism
Introns
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Mice
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
Transplantation, Heterologous
|
| IF |
6.304
|
| 引用数 |
9
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2 |
