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