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J Biol Chem. 2017 Sep 15;292(37):15395-15407. doi: 10.1074/jbc.M117.783738. Epub 2017 Aug 1.

The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186.

Author information

1
From the State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China and.
2
the State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China yelihong@nankai.edu.cn.
3
From the State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China and zhangxd@nankai.edu.cn.

Abstract

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 HMGA2 mRNA. 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.

KEYWORDS:

cell proliferation; hepatocellular carcinoma; high mobility group A2 (HMGA2); long noncoding RNA (long ncRNA, lncRNA); microRNA (miRNA); microRNA-186; oncogene; up-regulated in liver cancer (HULC)

PMID:
28765279
PMCID:
PMC5602398
DOI:
10.1074/jbc.M117.783738
[Indexed for MEDLINE]
Free PMC Article

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