同济大学发现甲状腺瘤致癌因子miR-155

　　

近日，同济大学的研究者发现了重要的甲状腺致癌因子——hsa-miR-155，可作为潜在的治疗或者诊断、预测恶性肿瘤甲状腺乳头状瘤（PCT）因子，相关研究成果发表在6月24的《The Journal of Clinical Endocrinology & Metabolism》杂志上。

甲状腺瘤是一种十分常见的癌症，常发生于40岁以下的人群，以20-40岁女性最常见。甲状腺瘤的癌变率高达10%-20%左右。甲状腺瘤难以根治，手术治疗术后极易复发，复发率高达90%以上。因此甲状腺瘤发病机制对癌症的有效治疗十分重要。

miRNA在许多肿瘤调控中扮演重要角色。有研究表明miR-155在脂肪肉瘤和乳腺癌中起重要作用，但是miR-155在PCT中调控作用仍知之甚少。

同济大学附属上海第十人民医院的研究者通过分析20对PTC患者和邻近的正常组织，评估miRNA表达水平，确认了miR-155促进肿瘤的生长。研究表明miR-155过表达（体外转染mimics，体内注射agomir，广州锐博生物提供），能显著促进PTC细胞的细胞活性和增殖。

这一研究显示miR-155作为PTC的致癌因子，通过靶向抑制APC基因的表达，进而激活Wnt/β-catenin信号，并调节下游基因c-Myc、cyclinD1、 TCF-1和LEF-1的表达。因此miR-155有望作为PCT的潜在治疗靶点。

随着肿瘤研究的深入，siRNA和miRNA已经成为基因研究的重要工具。锐博生物经验丰富的核酸研发团队已在相关领域开展了广泛的研究，并将继续精进科技，不断提升，为相关科研工作者提供更加方便的服务。

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锐博生物推荐原文摘要：

Upregulated miR-155 in papillary thyroid carcinoma promotes tumor growth by targeting APC and activating Wnt/β-catenin signaling

Xiaoping Zhang,Maoquan Li,et al. J CLIN ENDOCR METAB.June 24, 2013 jc.2012-3602.

Abstract:(Context) MicroRNAs (miRNAs) are strongly implicated in many cancers, including Papillary Thyroid Carcinoma (PTC), which is the most common malignancy in thyroid tissue. Recently, microRNA-155 (miR-155) has been proved to play a substantial role in liposarcoma and breast cancer, but its functions in the context of PTC remain unknown. (Objectives) The objective was to investigate the potential involvement of miR-155 in PTC. (Design) Expression levels of miR-155 were assessed via quantitative real-time PCR in 20 pairs of human PTC and adjacent normal tissues and in 4 human PTC cell lines. Lentiviral miR-155-overexpression models were performed in TPC-1 and CGTH-W3 cells, the effects on cell growth were evaluated. We have searched for miR-155 targets and identified the hypothesis that miR-155 could promote tumor growth of PTC by targeted regulating adenomatous polyposis coli (APC) expression and activating the Wnt/β-catenin signaling. (Results) MiR-155 levels were markedly increased in PTC specimens and PTC cell lines. Overexpression of miR-155 dramatically promoted PTC cell viability and colony formation in vitro, whereas miR-155 depletion reduced these parameters. Further studies revealed that adenomatous polyposis coli (APC) is a novel miR-155 target, as miR-155 bound directly to its 3’-UTR and reduced both the mRNA and protein levels of APC. Similar to the miR-155 over-expression, APC downregulation promoted cell growth, whereas rescued APC expression reversed the promotive effect of miR-155. Furthermore, miR-155 overexpression resulted in activation of β-catenin and induction of several downstream genes including c-Myc, cyclinD1, TCF-1 and LEF-1. Depletion of β-catenin partially prevented miR-155-induced tumor cell viability and colony formation. In xenograft animal experiments, we found overexpressed miR-155 effectively promoted tumor growth of PTC cells. (Conclusions)Our results indicate that miR-155 functions as an oncogene in PTC. By targeting APC, miR-155 efficiently regulates the Wnt/β-catenin signaling.