Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 292, Issue 37, Pages 15395-15407Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.783738
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Funding
- National Basic Research Program of China 973 Program [2015CB553703, 2015CB553905]
- National Natural Science Foundation of China [81272218, 81372186, 31670769, 31670771]
- Project of Prevention and Treatment of Key Infectious Diseases Grant [2014ZX0002002-005]
- Project of Prevention and Control of Key Chronic Non-infectious Diseases Grant [2016YFC130340]
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The long noncoding RNA highly up-regulated in liver cancer (HULC) is aberrantly elevated in hepatocellular carcinoma (HCC), and this up-regulation is crucial for HCC pathogenesis. However, the underlying mechanism in HULC up-regulation is poorly understood. We hypothesized that HULC might modulate the oncogene high mobility group A2 (HMGA2) to promote hepatocarcinogenesis. Quantitative real-time PCR analysis showed that the expression levels of HULC were positively correlated with those of HMGA2 in clinical HCC tissues. Interestingly, we also observed that HULC could up-regulate HMGA2 in HCC cells. Mechanistically, we found that the microRNA-186 inhibited HMGA2 expression by targeting the 3'-untranslated region (3'-UTR) of HMGA2m RNA. Strikingly, HULC acted as a competing noncoding RNA to sequester miR-186 and thereby relieved miR-186-mediated HMGA2 repression. Functionally, HMGA2 knockdown decreased the HULC-enhanced growth of HCC cells both in vitro and in vivo. We conclude that the long noncoding RNA HULC increases HMGA2 expression by sequestering miR-186 post-transcriptionally and thereby promotes liver cancer growth, providing new insights into the mechanism by which HULC enhances hepatocarcinogenesis.
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