RGD Reference Report - miR-22 promotes HBV-related hepatocellular carcinoma development in males. - Rat Genome Database

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miR-22 promotes HBV-related hepatocellular carcinoma development in males.

Authors: Jiang, Runqiu  Deng, Lei  Zhao, Liang  Li, Xiangcheng  Zhang, Feng  Xia, Yongxiang  Gao, Yun  Wang, Xuehao  Sun, Beicheng 
Citation: Jiang R, etal., Clin Cancer Res. 2011 Sep 1;17(17):5593-603. doi: 10.1158/1078-0432.CCR-10-1734. Epub 2011 Jul 12.
RGD ID: 14700876
Pubmed: (View Article at PubMed) PMID:21750200
DOI: Full-text: DOI:10.1158/1078-0432.CCR-10-1734

PURPOSE: Previous reports have shown that IL-1α-MyD88-IL-6 signaling is essential in promoting hepatocellular carcinoma (HCC) development in a diethylnitrosamine (DEN)-induced mouse model. We aimed to determine whether interleukin (IL)-1α regulates HCC development in humans.
METHODS: HBV-associated HCC tissue, corresponding adjacent tissue, and normal tissue samples were obtained from 80 male and 36 female patients. IL-1α, ERα, IL-6, and MyD88 were quantified by using real-time PCR and Western blot. Stem-loop PCR was used to quantify miR-22 expression. Luciferase reporter assays were used to study transcriptional regulation.
RESULTS: IL-1α was highly expressed in male tumor adjacent tissue compared with normal tissue (P = 0.025); however, this was not the case for female subjects. A linear relationship was observed between increased IL-1α and decreased ERα expression in male tumor adjacent tissue (r = -0.616, P = 0.004). Our results also indicated that estrogen (E2) was suppressed upon IL-1α secretion in ERα-overexpressed HCC cells. We detected high expression of miR-22 in male tumor adjacent tissue compared with controls (P = 0.027); furthermore, we showed that miR-22 downregulates ERα transcription by targeting the 3'-untranslated region. In the DEN-induced model, IL-1α was highly expressed in sprouting tumors and gradually decreased in conjunction with HCC development.
CONCLUSION: Overexpression of miR-22 in male tumor adjacent tissue was associated with downregulated ERα expression, potentially by attenuating the protective effect of estrogen and causing increased IL-1α expression. These results may explain the high incidence of HBV-associated HCC in the male population.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mir22  (microRNA 22)

Genes (Mus musculus)
Mir22  (microRNA 22)

Genes (Homo sapiens)
MIR22  (microRNA 22)

Additional Information