Expression and role of miRNA in renal cell carcinoma which resists to immunotherapy

miRNA在免疫治疗抵抗性肾细胞癌中的表达及作用

• 批准号: 22591773
• 负责人: ISHIBASHI Kei
• 金额: $ 2.33万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591773/
• 关键词: 腫瘍学; 腎癌; インターフェロン; IL-6; SOCS3; miRNA

Interferon (IFN)-α is one of the most commonly used agents in immunotherapy for patients with advanced -stage renal cell carcinoma. However, because of the drug resistance to IFN-α, its benefits are limited. In this study, we evaluated theexpression of hsa-miR-93 or SOCS3-mRNA in renal cell carcinoma cells which resists to IFN treatment. Among the renal cell carcinoma cell lines which we used in this study, 786-O cells showed resistance to IFN treatment. The expression of both hsa-miR-93 and SOCS3-mRNA was significantly higher compared with other cell lines. Suppression of hsa-miR-93 or SOCS3-mRNA induced sensitivity to IFN in 786-O cells. Especially, down regulation of SOCS3-mRNA enhanced STAT1 activation and anti-tumor activity of IFN, both in vitro and in vivo, in a human IFN- resistant RCC cell line 786-O. Because IL-6 receptor antibody blocked SOCS3 efficiently, combination therapy using an antihuman IL-6R antibody with IFN-α may represent a novel therapeutic approach for the treatment of renal cell carcinoma.

干扰素（IFN）-α是患有晚期肾细胞癌患者免疫疗法中最常用的药物之一。但是，由于对IFN-α的耐药性，其益处受到限制。在这项研究中，我们评估了肾细胞癌细胞中HSA-MIR-93或SOCS3-MRNA的表达，该细胞抗IFN治疗。在我们在这项研究中使用的肾细胞癌细胞系中，有786-O细胞表现出对IFN治疗的抗性。与其他细胞系相比，HSA-MIR-93和SOCS3-MRNA的表达显着高。抑制HSA-MIR-93或SOCS3-MRNA诱导对786-O细胞IFN的敏感性。尤其是，在人IFN耐药的RCC细胞系786-O中，下调SOCS3-MRNA增强了IFN的STEC1增强的IFN和体内IFN的抗肿瘤活性。由于IL-6受体抗体有效地阻断了SOCS3，因此使用抗人IL-6R抗体与IFN-α的联合治疗可能代表一种用于治疗肾细胞癌的新型治疗方法。

项目成果

IL-6 and SOCS3 regulates cell proliferation in renal cell carcinoma cells

IL-6 和 SOCS3 调节肾细胞癌细胞增殖

• 发表时间: 2013
• 作者: 宮里実;與那嶺智子,泉惠一朗,宮城亮太,芦刈明日香,仲西昌太郎,木村隆,松村英理,大城琢磨,呉屋真人,斎藤誠一;松本 洋明;Kei Ishibashi;Kei Ishibashi;石橋 啓;石橋 啓;Kei Ishibashi;石橋 啓;石橋 啓;Ishibashi K
• 通讯作者: Ishibashi K