Journal article
MicroRNA‐494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer
Hepatology (Baltimore, Md.), Vol.59(1), pp.202-215
01/2014
DOI: 10.1002/hep.26662
PMCID: PMC3877416
PMID: 23913442
Abstract
Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver's unique affinity for small nucleic acids, miRNA‐based therapy has been proposed in the treatment of liver disease. Thus, there is an urgent need to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCCs. We identified an up‐regulated miRNA megacluster comprised of 53 miRNAs on mouse chromosome 12qF1 (human homolog 14q32). This miRNA megacluster is up‐regulated in all three transgenic liver models and in a subset of human HCCs. An unbiased functional analysis of all miRNAs within this cluster was performed. We found that miR‐494 is overexpressed in human HCC and aids in transformation by regulating the G1/S cell cycle transition through targeting of the Mutated in Colorectal Cancer tumor suppressor. miR‐494 inhibition in human HCC cell lines decreases cellular transformation, and anti‐miR‐494 treatment of primary MYC‐driven liver tumor formation significantly diminishes tumor size. Conclusion: Our findings identify a new therapeutic target (miR‐494) for the treatment of HCC. (Hepatology 2014;58:202–215)
Details
- Title: Subtitle
- MicroRNA‐494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer
- Creators
- Lionel Lim - University of California San FranciscoAsha Balakrishnan - Hannover Medical SchoolNoelle Huskey - University of California San FranciscoKirk D Jones - University of California San FranciscoMona Jodari - University of California San FranciscoRaymond Ng - University of California San FranciscoGuisheng Song - University of California San FranciscoJesse Riordan - University of IowaBrittany Anderton - University of California San FranciscoSiu‐Tim Cheung - The University of Hong KongHolger Willenbring - University of California San FranciscoAdam Dupuy - University of IowaXin Chen - University of California San FranciscoDavid Brown - Mirna Therapeutics (United States)Aaron N Chang - Baylor Institute for Immunology ResearchAndrei Goga - University of California San Francisco
- Resource Type
- Journal article
- Publication Details
- Hepatology (Baltimore, Md.), Vol.59(1), pp.202-215
- DOI
- 10.1002/hep.26662
- PMID
- 23913442
- PMCID
- PMC3877416
- NLM abbreviation
- Hepatology
- ISSN
- 0270-9139
- eISSN
- 1527-3350
- Number of pages
- 14
- Language
- English
- Date published
- 01/2014
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025316002771
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