Line-1: Implications in the etiology of cancer, clinical applications, and pharmacologic targets.
Mutat Res Rev Mutat Res
; 778: 51-60, 2018.
Article
de En
| MEDLINE
| ID: mdl-30454683
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 â¼100 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Génome humain
/
Éléments LINE
/
Thérapie moléculaire ciblée
/
Tumeurs
Type d'étude:
Etiology_studies
Limites:
Humans
Langue:
En
Journal:
Mutat Res Rev Mutat Res
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique