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| Status |
Public on Dec 05, 2018 |
| Title |
Characterization of microRNA-493-5p targets in liver cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| |
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| Overall design |
To identify miR-493-5p targets, Hep3B and HepG2 cells were transfected using miR-493-5p and negative control miRNA mimics.
|
| Web link |
https://www.nature.com/articles/s41419-019-1788-6
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| |
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| Contributor(s) |
Gailhouste L, Ochiya T |
| Citation(s) |
31320614, 31883160 |
| |
| Submission date |
Dec 04, 2018 |
| Last update date |
Mar 16, 2020 |
| Contact name |
Luc Gailhouste |
| E-mail(s) |
luc.gailhouste@riken.jp
|
| Organization name |
RIKEN
|
| Department |
Cluster for Pioneering Research
|
| Lab |
Liver Cancer Prevention Research Unit
|
| Street address |
408 Main Research Building, 2-1 Hirosawa
|
| City |
Wako |
| State/province |
Saitama |
| ZIP/Postal code |
351-0198 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA508299 |
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