Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas

• Published in: Cancer cell international Vol. 20; no. 1; p. 426
• Main Authors: Shademan, Milad, Zare, Khadijeh, Zahedi, Morteza, Mosannen Mozaffari, Hooman, Bagheri Hosseini, Hadi, Ghaffarzadegan, Kamran, Goshayeshi, Ladan, Dehghani, Hesam
• Format: Journal Article
• Language: English
• Published: England BioMed Central 01.09.2020; BMC
• Subjects: Adenocarcinoma; Adenoma; Binding sites; Biopsy; Cloning; Colorectal adenocarcinoma; Colorectal adenoma; Colorectal cancer; Colorectal carcinoma; Copy number; CpG islands; Deoxyribonucleic acid; DNA; DNA methylation; Genomes; Insertion; LINE-1; Methylation; Polymerase chain reaction; Primary Research; Proteins; Quantitative analysis; Retrotransposition; RNA polymerase; Sodium; Tumors; Whole genome sequencing; Iran; Asia; United States > US; Insertion; LINE-1; Colorectal adenoma; Retrotransposition; Methylation; Colorectal adenocarcinoma
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-020-01511-5

The methylation of the CpG islands of the LINE-1 promoter is a tight control mechanism on the function of mobile elements. However, simultaneous quantification of promoter methylation and transcription of LINE-1 has not been performed in progressive stages of colorectal cancer. In addition, the insertion of mobile elements in the genome of advanced adenoma stage, a precancerous stage before colorectal carcinoma has not been emphasized. In this study, we quantify promoter methylation and transcripts of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma. In addition, we analyze the insertion of LINE-1, Alu, and SVA elements in the genome of patient tumors with colorectal advanced adenomas. LINE-1 hypomethylation status was evaluated by absolute quantitative analysis of methylated alleles (AQAMA) assay. To quantify the level of transcripts for LINE-1, quantitative RT-PCR was performed. To find mobile element insertions, the advanced adenoma tissue samples were subjected to whole genome sequencing and MELT analysis. We found that the LINE-1 promoter methylation in advanced adenoma and adenocarcinoma was significantly lower than that in non-advanced adenomas. Accordingly, the copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas. Whole-genome sequencing analysis of colorectal advanced adenomas revealed that at this stage polymorphic insertions of LINE-1, Alu, and SVA comprise approximately 16%, 51%, and 74% of total insertions, respectively. Our correlative analysis showing a decreased methylation of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and polymorphic genomic insertions in advanced adenoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.