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miR-22 Promotes HBV-Related Hepatocellular Carcinoma Development in Males

dangdang 添加于 2011-11-24 21:31 | 1438 次阅读 | 0 个评论

作者
Jiang R, Deng L, Zhao L, Li X, Zhang F, Xia Y, Gao Y, Wang X, Sun B
摘要
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.
详细资料
- 文献种类:期刊
- 期刊名称: Clinical Cancer Research
- 期刊缩写: Clinical Cancer Research
- 期卷页: 2011年第17卷第17期 5593-5603页
- ISBN: 1078-0432
标签

miR22
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