miR-122主要是在肝細(xì)胞中發(fā)現(xiàn)的,，在肝細(xì)胞中，它是最為豐富的microRNA,，并且在調(diào)節(jié)體內(nèi)膽固醇方面發(fā)揮著主要作用,。然而，在一些患有肝細(xì)胞癌的病人體內(nèi),。這種microRNA丟失導(dǎo)致預(yù)后不良(poor prognosis),。在一項(xiàng)新的動(dòng)物研究中，來(lái)自美國(guó)俄亥俄州立大學(xué)綜合癌癥中心的研究人員發(fā)現(xiàn)肝細(xì)胞中一種被稱(chēng)作miR-122的microRNA(miR)丟失可能導(dǎo)致肝癌產(chǎn)生,，而且恢復(fù)這種分子可能延緩腫瘤生長(zhǎng),，從而一種新的方法來(lái)治療這種疾病。相關(guān)研究結(jié)果發(fā)表在Journal of Clinical Investigation期刊上,。
研究人員研究了當(dāng)肝細(xì)胞缺乏一種被稱(chēng)作microRNA-122(miR-122)的分子時(shí)會(huì)發(fā)生什么,。他們發(fā)現(xiàn)當(dāng)這種分子丟失時(shí)，肝臟產(chǎn)生脂肪沉積,、炎癥和類(lèi)似肝細(xì)胞癌(hepatocellular carcinoma, HCC)的腫瘤,，其中肝細(xì)胞癌是一種最為常見(jiàn)形式的肝癌。
當(dāng)研究人員通過(guò)將miR-122基因?qū)敫渭?xì)胞來(lái)人工恢復(fù)miR-122到接近正常水平,，它能夠顯著性地降低腫瘤的大小和數(shù)量：在經(jīng)過(guò)處理的動(dòng)物體內(nèi),，腫瘤占肝臟平均表面積的8%，而在未接受處理的對(duì)照動(dòng)物體內(nèi),，腫瘤所占比例為40%,。
這些發(fā)現(xiàn)揭示miR-122在健康肝臟中發(fā)揮著至關(guān)重要的腫瘤抑制性作用，而且對(duì)一些患有肝癌的病人而言,，這也可能著重強(qiáng)調(diào)了加入miR-122所發(fā)揮的治療性作用,。(生物谷：Bioon.com)
本文編譯自L(fǎng)oss of Tiny Liver Molecule Might Lead to Liver Cancer
doi: 10.1172/JCI63539
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Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
1.Shu-hao Hsu, Bo Wang, Janaiah Kota, Jianhua Yu, Stefan Costinean, Huban Kutay, Lianbo Yu, Shoumei Bai, Krista La Perle, Raghu R. Chivukula, Hsiaoyin Mao, Min Wei, K. Reed Clark, Jerry R. Mendell, Michael A. Caligiuri, Samson T. Jacob, Joshua T. Mendell, Kalpana Ghoshal
miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.
