Line1: Implications in the Etiology of Human Diseases, Clinical Utilities, and Pharmacological Target for Disease Treatment

Abstract

Long interspersed nuclear elements-1 (Line-1 or L1) accounts for approximately 17% of the human genome. The majority of L1s are inactive, but ~100 remain retrotransposon competent (RC-L1) and retrotranspose through RNA intermediates to different locations of the genome. It is well established that L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt loci (e.g. gene structure) in ways that lead to human disease, and activities of L1 si/piRNA, ORF1 and ORF2 proteins are implicated in the etiology and progression of human diseases such as in breast and colon cancer (Miki et al., 1992; Ohms et al., 2014). Despite these implications, very little is known about pharmacological molecules that inhibit and reverse L1’s harmful effects. The clinical utility of L1 as a player in tumorigenesis and as a biomarker for disease initiation and progression is not thoroughly understood. In this review, we analyzed the life cycle of L1, its roles in disease initiation and progression, clinical utilities and potential as a pharmacological target and a biomarker for the diagnosis and treatment of human diseases, such as cancer.