LINE-1 in cancer: multifaceted functions and potential clinical implications.
Long interspersed nuclear element-1 (L1) retrotransposons are jumping genes that comprise 17% of human DNA. They utilize a ''copy-and-paste'' mechanism to propagate themselves throughout the genome via RNA intermediates, a process termed retrotransposition. L1s are active in the germ line and during embryogenesis, yet they are epigenetically suppressed in somatic cells. In cancer cells, however, L1s are aberrantly activated and may have a role in genome instability, one of the hallmarks of cancer pathogenesis. Their methylation states and retrotransposition activities are associated with and fluctuate during cancer initiation and progression, thus representing promising diagnostic biomarkers and therapeutic targets. During tumorigenesis, L1s exert both retrotransposition-dependent and retrotransposition-independent functions. The former may result in alterations in target gene expression or chromosomal rearrangement, or drive Alu and SVA, events that could function in tumorigenesis, whereas the latter can potentially exert epigenetic regulation by generating endo-siRNAs, forming chimeric L1 transcripts or changing the expression of adjacent genes by providing novel splicing sites or alternative promoters. Moreover, the L1 encoded proteins, ORF1p and ORF2p, may have pro-oncogenic potential by, for example, activating oncogenic transcriptional factors or sequestering oncosuppressors. Herein, we introduce the components and mechanisms of L1 retrotransposition, discuss the landscape, possible functions, and regulation of L1 activity in cancer, and seek their potential as diagnostic biomarkers and therapeutic targets.Genet Med 18 5, 431-439.
Department of Gastroenterology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, China.
Lu
L
Xiao-Jie
The Reproductive Center, Jiangsu Huai'an Maternity and Children Hospital, Huai'an, China.
Xue
X
Hui-Ying
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Xiaolong
X
Qi
Department of Rehabilitation, Affiliated Huai'an Hospital of Xuzhou Medical College and Second People's Hospital of Huai'an, Huai'an, China.
Xu
X
Jiang
Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
Ma
M
Shi-Jie
D044127:Epigenesis, Genetic; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D018626:Retroelements / Q000235:genetics
D011506:Proteins; D034741:RNA, Small Interfering; D018626:Retroelements