Line-1: Implications in the etiology of cancer, clinical applications, and pharmacologic targets

M Khalid; P Bojang Jr; A A I Hassanin; E C Bowers; E M Reyes-Reyes; I N Ramos; K S Ramos

doi:10.1016/j.mrrev.2018.09.003

Line-1: Implications in the etiology of cancer, clinical applications, and pharmacologic targets

Mutat Res Rev Mutat Res. 2018 Oct-Dec:778:51-60. doi: 10.1016/j.mrrev.2018.09.003. Epub 2018 Sep 19.

Authors

M Khalid¹, P Bojang Jr¹, A A I Hassanin², E C Bowers¹, E M Reyes-Reyes¹, I N Ramos³, K S Ramos⁴

Affiliations

¹ Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, College of Medicine, Tucson, University of Arizona, USA.
² Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, College of Medicine, Tucson, University of Arizona, USA; Department of Animal Wealth Development, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
³ Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, USA; Center for Applied Genetics and Genomic Medicine, University of Arizona, USA.
⁴ Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, College of Medicine, Tucson, University of Arizona, USA; Center for Applied Genetics and Genomic Medicine, University of Arizona, USA; Department of Medicine, Division of Clinical Decision Support and Data Analytics, College of Medicine, Phoenix, University of Arizona, USA. Electronic address: ksramos@email.arizona.edu.

PMID: 30454683
DOI: 10.1016/j.mrrev.2018.09.003

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 able to retrotranspose through RNA intermediates to different locations of the genome. L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt genetic loci at sites of insertion, while the activities of L1 si/piRNAs, mRNAs, and ORF1 and ORF2 proteins, and have been implicated in the etiology and progression of several human diseases. Despite these relationships, little is known about the clinical utility of L1 as a biomarker of disease initiation and progression, or the utility of small molecules to inhibit and reverse the harmful effects of L1. In this review, we discuss the life cycle of L1, somatic and germline inhibitions, the mechanisms of L1 retrotransposition dependent and independent disease initiation and progression, clinical utilities, and potential of L1s as pharmacologic targets for the treatment of cancer.

Keywords: Biomarker; EMT; Pharmacology; Retrotransposition; ceRNAs.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Endonucleases / genetics
Genome, Human / genetics*
Humans
Long Interspersed Nucleotide Elements / genetics*
Molecular Targeted Therapy*
Neoplasms / genetics*
Neoplasms / therapy
Proteins / genetics
RNA, Small Interfering / genetics
RNA-Directed DNA Polymerase / genetics

Substances

ORF1 protein, human
ORF2 protein, human
Proteins
RNA, Small Interfering
RNA-Directed DNA Polymerase
Endonucleases