title: Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide.
abstract: The typical progression of oral cancer is from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. It is important to investigate malignant oral cancer progression and development in order to determine useful approaches of prevention of dysplastic lesions. The present study aimed to gain insights into the underlying molecular mechanism of oral carcinogenesis by establishing a rat model of oral carcinogenesis using 4‑nitroquinoline 1‑oxide. Subsequently, transcription profile analysis using an integrating microarray was performed. The dynamic gene expression changes of the six stages of rat oral carcinogenesis (normal, mild epithelial dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ and oral squamous cell carcinomas) were analyzed using component plane presentations (CPP)‑self‑organizing map (SOM). Six genes were verified by quantitative polymerase chain reaction, immunohistochemistry and succinate dehydrogenase (SDH) activity assay kit. Numerous differentially expressed genes (DEGs) were identified during rat oral carcinogenesis. CPP‑SOM determined that these DEGs were primarily enriched during cell cycle, apoptosis, inflammatory response and tricarboxylic acid cycle, indicating the coordinated regulation of molecular networks. In addition, the expression of specific DEGs, such as janus kinase 3, cyclin‑dependent kinase A‑1, B‑cell chronic lymphocytic leukaemia/lymphoma 2‑like 2, nuclear factor‑κB, tumor necrosis factor receptor superfamily member 1A, cyclin D1 and SDH were identified to have high concordance with the results from microarray data. The current study demonstrated that oral carcinogenesis is a multi‑step and multi‑gene process, with a distinct pattern alteration along a continuum of malignant transformation. In addition, this comprehensive investigation provided a theoretical basis for the understanding of the molecular alterations associated with oral carcinogenesis.
authors: Department of Oral Mucosal Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors: Shuyun
authors: S
authors: Ge
authors: State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors: Ji
authors: J
authors: Zhang
authors: State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors: Yanzhi
authors: Y
authors: Du
authors: State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors: Bin
authors: B
authors: Hu
authors: Department of Oral Mucosal Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors: Zengtong
authors: Z
authors: Zhou
authors: Department of Stomatology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors: Jianing
authors: J
authors: Lou
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014062:Tongue Neoplasms / Q000235:genetics / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D059467:Transcriptome
chemical_list: C530106:Ccnd1 protein, rat; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D019938:Cyclin D1; D015112:4-Nitroquinoline-1-oxide; D013385:Succinate Dehydrogenase