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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mir22  (microRNA 22)

Genes (Mus musculus)
Mir22  (microRNA 22)

Genes (Homo sapiens)
MIR22  (microRNA 22)


Additional Information