title: Modulation of IL-1β reprogrammes the tumor microenvironment to interrupt oral carcinogenesis.
abstract: Head and neck squamous cell carcinoma (HNSCC) development is a multistage process includes the normal, dysplasia and squamous cell carcinoma (SCC) stages. Recently, increasing evidence has suggested that the tumor microenvironment (TME) is an integral part of malignant transformation. Exploring certain key node genes in TME for future intervention in dysplasia to interrupt oral carcinogenesis was the primary goal of this research. To achieve this goal, systems biology approaches were first applied to the epithelia and fibroblasts collected at sequential stages in a 4-nitroquinoline-1-oxide (4NQO) -induced rat oral carcinogenesis model. Through bioinformatics network construction, IL-1β was identified as one of the key node genes in TME during carcinogenesis. Immunohistochemical staining of human and rat samples demonstrated that IL-1β expression patterns were parallel to the stages of malignant transformation. Silencing IL-1β with lentivirus-delivered shRNA significantly inhibited oral squamous cell carcinoma cell growth both in vivo and in vitro. Based on these findings, we hypothesized that IL-1β may be a chemoprevention target in TME during oral carcinogenesis. Therefore, we targeted IL-1 in the TME by oral mucosal injection of an IL-1 receptor antagonist in 4NQO rats. The results demonstrated that targeting IL-1 could interrupt oral carcinogenesis by reprogramming the TME.
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qinchao
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000008:administration & dosage / Q000009:adverse effects; D000284:Administration, Oral; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts; D020869:Gene Expression Profiling; D020868:Gene Silencing; D064593:Heterografts; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D053583:Interleukin-1beta; D015112:4-Nitroquinoline-1-oxide
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