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miR-204 通过阻断 JAK2-STAT3 信号通路抑制头颈部鳞状细胞癌细胞的血管生成并增加对西妥昔单抗的敏感性。

miR-204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAK2-STAT3 signaling.

机构信息

Department of Otolarynglogy Head & Neck Surgery, Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639th on Huangpu District Manufacturing Bureau Road, Shanghai, 200011, China; Ear Institute Shanghai Jiaotong University School of Medicine.

Department of Otolarynglogy Head & Neck Surgery, Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639th on Huangpu District Manufacturing Bureau Road, Shanghai, 200011, China; Ear Institute Shanghai Jiaotong University School of Medicine.

出版信息

Biomed Pharmacother. 2018 Mar;99:278-285. doi: 10.1016/j.biopha.2018.01.055.

Abstract

This study aims to investigate the roles of miR-204 in tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was reduced in HNSCC tissues relative to that in normal adjacent tissues. Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells. Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204 overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2 attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore, overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204 acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells.

摘要

本研究旨在探讨 miR-204 在头颈部鳞状细胞癌(HNSCC)肿瘤血管生成中的作用。在这里,我们发现 miR-204 的水平在 HNSCC 组织中相对于正常相邻组织降低。miR-204 的过表达促进了 HNSCC 细胞中的肿瘤血管生成。机制上,JAK2 被鉴定为 miR-204 的直接靶标,miR-204 的过表达阻断了 JAK2/STAT3 通路。此外,JAK2 的过表达减弱了 miR-204 对 HNSCC 肿瘤血管生成的抑制作用。此外,miR-204 的过表达增强了 HNSCC 细胞中西妥昔单抗的敏感性,JAK2 的过表达也减弱了这种作用。重要的是,JAK2 的表达与 HNSCC 组织中 miR-204 的水平呈负相关。因此,miR-204 通过阻断 HNSCC 细胞中的 JAK2/STAT3 通路发挥肿瘤抑制作用。

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