Publication: Patterns and possible roles of LINE-1 methylation changes in smoke-exposed epithelia.
Accepted Date
2012-08-15
Issued Date
2012-09-18
Resource Type
Language
eng
ISSN
1932-6203 (electronic)
Rights
Mahidol University
Rights Holder(s)
Public Library of Science
Bibliographic Citation
Wangsri S, Subbalekha K, Kitkumthorn N, Mutirangura A. Patterns and possible roles of LINE-1 methylation changes in smoke-exposed epithelia. PLoS One. 2012;7(9):e45292.
Suggested Citation
Nakarin Kitkumthorn, นครินทร์ กิตกำธร, Siriporn Wangsri, ศิริพร วังศรี, Keskanya Subbalekha, เกศกัญญา สัพพะเลข, Apiwat Mutirangura, อภิวัฒน์ มุทิรางกูร Patterns and possible roles of LINE-1 methylation changes in smoke-exposed epithelia.. Wangsri S, Subbalekha K, Kitkumthorn N, Mutirangura A. Patterns and possible roles of LINE-1 methylation changes in smoke-exposed epithelia. PLoS One. 2012;7(9):e45292.. doi:10.1371/journal.pone.0045292 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/932
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Title
Patterns and possible roles of LINE-1 methylation changes in smoke-exposed epithelia.
Corresponding Author(s)
Abstract
Tobacco smoking and reduced methylation of long interspersed element-1 (LINE-1) are crucial in oral carcinogenesis. 5'UTR of human LINE-1 sequence contains several CpG dinucleotides which are methylated in various proportions (0-100%). Methylation levels of many LINE-1s in cancer were reduced, hypomethylated. The hypomethylation of each LINE-1 locus can promote instability of genome and repress expression of a gene located on that same chromosome. This study investigated if cigarette smoking influences LINE-1 methylation of oral mucosal cells. The methylation of human LINE-1 in clinically normal oral mucosa of current smokers was compared to non-smokers. By using the combined bisulphite restriction analysis, each LINE-1 sequence was categorised into 4 patterns depending on the methylation status and location of the two 18-bp successive CpG from 5' to 3' including (m)C(m)C, (u)C(u)C, (m)C(u)C and (u)C(m)C. Of these, (m)C and (u)C represent methylated and unmethylated CpG, respectively. The DNA bisulphite sequence demonstrated that most CpGs of (m)C(m)C and (u)C(u)C were methylated and unmethylated, respectively. Nevertheless, some CpGs of each (m)C(u)C or (u)C(m)C allele were methylated. Imaging of the digestion products was used to generate %methylation value. No significant difference in the overall LINE-1 methylation level but the differences in percentages of some methylation patterns were discovered. The %(m)C(m)C and %(u)C(u)C increased, while the %(m)C(u)C decreased in current smokers (p = 0.002, 0.015, and <0.0001, respectively). Additionally, the lower %(m)C(u)C still persisted in persons who had stopped smoking for over 1 year (p = 0.001). The %(m)C(u)C also decreased in the higher pack-year smokers (p = 0.028). Smoking possibly altered (m)C(u)C to (m)C(m)C and (u)C(u)C forms, and changes (u)C(m)C to (u)C(u)C forms. In conclusion, smoking changes methylation levels of partial methylated LINE-1s and increased the number of hypo- and hypermethylated loci. These hypomethylated LINE-1s may possess carcinogenesis potential. Moreover, LINE-1 methylation patterns may be useful for monitoring oral carcinogenesis in smokers.