机构:[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, Sec.3, Renminnan Road, Chengdu 610041, Sichuan, China.[2]State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, Shandong, China.[3]Department of Head and Neck Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, Sichuan, China.外科中心头颈外科中心四川省人民医院四川省肿瘤医院头颈外科
Background Human papillomavirus (HPV)-positive oral squamous cell carcinoma (OSCC) is increasing worldwide with typically higher grade and stage, while better prognosis. microRNAs (miRNAs) has been shown to play a critical role in cancer, however, their role in HPV-positive OSCC progression remains unclear. Methods miRNA microarray was performed to identify differentially expressed miRNAs. qRT-PCR and FISH were performed to determine the relative expression of miR-550a-3-5p. CCK-8, Flow cytometry, Wound healing, Cell invasion assays and xenograft experiments were conducted to analyze the biological roles of miR-550a-3-5p. Tumor-associated macrophages (TAMs) generation, co-culturing of cancer cells with TAMs, Western blot, Dual-luciferase reporter gene assay, Immunohistochemistry and animal studies were performed to explore the mechanisms underlying the functions of miR-550a-3-5p. Results We identified 19 miRNAs differentially expressed in HPV-positive OSCC specimens and miR-550a-3-5p was down-regulated. The low expression of miR-550a-3-5p correlated with higher tumor size and nodal metastasis of HPV-positive OSCC patients. Then, we found that miR-550a-3-5p suppressed the migration, invasion and EMT of HPV-positive OSCC cells dependent on decreasing M2 macrophages polarization. Moreover, miR-550a-3-5p, down-regulated by E6 oncoprotein, inhibited M2 macrophages polarization by YAP/CCL2 signaling, which in turn abrogating EMT program in HPV-positive OSCC cells. In addition, in both xenografts and clinical HPV-positive OSCC samples, miR-550a-3-5p levels were inversely associated with YAP, CCL2 expressions and the number of M2 macrophages. Conclusions E6/miR-550a-3-5p/YAP/CCL2 signaling induces M2 macrophages polarization to enhance EMT and progression, revealing a novel crosstalk between cancer cells and immune cells in HPV-positive OSCC microenvironment.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81672672, 81972542, 81902779, 21838002]; National Key R&D Program of China [2019YFA09005700]
第一作者机构:[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, Sec.3, Renminnan Road, Chengdu 610041, Sichuan, China.
通讯作者:
推荐引用方式(GB/T 7714):
Ming-xin Cao,Wei-long Zhang,Xiang-hua Yu,et al.Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2020,39(1):doi:10.1186/s13046-020-01602-1.
APA:
Ming-xin Cao,Wei-long Zhang,Xiang-hua Yu,Jia-shun Wu,Xin-wei Qiao...&Ya-ling Tang.(2020).Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,39,(1)
MLA:
Ming-xin Cao,et al."Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 39..1(2020)