title: Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.
abstract: Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, No. 250 Kao-Kuang Road, Taichung 402, Taiwan.
authors.forename: Zi-Lun
authors.identifier: 0000-0003-4433-7011
authors.initials: ZL
authors.lastname: Lai
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, No. 250 Kao-Kuang Road, Taichung 402, Taiwan ; Department of Otolaryngology Head and Neck Surgery, China Medical University, Taichung 404, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Yung-An
authors.initials: YA
authors.lastname: Tsou
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91 Hsueh-Shih Road, Taichung 404, Taiwan.
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, China Medical University, Taichung 404, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Bioresources, Da-Yeh University, Changhwa 515, Taiwan.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Chang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91 Hsueh-Shih Road, Taichung 404, Taiwan.
authors.forename: Ju-Chien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, No. 250 Kao-Kuang Road, Taichung 402, Taiwan ; Rong Hsing Research Center for Translational Medicine, iEGG Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Chuan-Mu
authors.identifier: 0000-0003-2461-9150
authors.initials: CM
authors.lastname: Chen
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D001114:Areca; D001115:Arecoline; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
chemical_list: D002273:Carcinogens; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D001115:Arecoline; D015112:4-Nitroquinoline-1-oxide; D008780:Methyltransferases