hsa-miR-191 Is a Candidate Oncogene Target for Hepatocellular Carcinoma Therapy
hsa-miR-191 Is a Candidate Oncogene Target for Hepatocellular Carcinoma Therapy
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DOI：
10.1158/0008-5472.can-10-1313
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发表时间：
2010-10-15
期刊：
影响因子：
11.2
通讯作者：
Yerushalmi, Noga
中科院分区：
文献类型：
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作者：
Elyakim, Eran;Sitbon, Einat;Yerushalmi, Noga
由于缺乏有效的治疗方案，肝细胞癌（HCC）通常是一种致命的疾病。在HCC细胞中发挥多效性作用的致癌microRNA的鉴定可能提供新的治疗靶点。在这项研究中，我们已经确定了人类microRNA miR-191作为HCC治疗的潜在靶点。在HCC原位异种移植小鼠模型中，miR-191的抑制在体外降低了细胞增殖并诱导了细胞凋亡，在体内显著降低了肿瘤质量。此外，发现miR-191被二恶英（一种已知的肝脏致癌物）上调，并被发现是多种癌症相关途径的调节剂。我们的研究结果为miR-191靶向作为改善HCC治疗的合理策略提供了临床前概念证明。Cancer Res; 70（20）; 8077-87. (C)2010年AACR。
Hepatocellular carcinoma (HCC) is generally a fatal disease due to a paucity of effective treatment options. The identification of oncogenic microRNAs that exert pleiotropic effects in HCC cells may offer new therapeutic targets. In this study, we have identified the human microRNA miR-191 as a potential target for HCC therapy. Inhibition of miR-191 decreased cell proliferation and induced apoptosis in vitro and significantly reduced tumor masses in vivo in an orthotopic xenograft mouse model of HCC. Additionally, miR-191 was found to be upregulated by a dioxin, a known liver carcinogen, and was found to be a regulator of a variety of cancer-related pathways. Our findings offer a preclinical proof of concept for miR-191 targeting as a rational strategy to pursue for improving HCC treatment. Cancer Res; 70(20); 8077-87. (C) 2010 AACR.