LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies.
Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both "risk" and "protective" splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by theOLR1gene. WhenOLR1undergoes AS events, it generates three variants:OLR1,OLR1D4andLOXIN.The latter lacks exon 5 and two-thirds of the functional domain. Literature data demonstrate a protective role of LOXIN in pathologies correlated with LOX-1 overexpression such as atherosclerosis and tumors. In this review, we summarize recent developments in understanding ofOLR1AS while also highlighting data warranting further investigation of this process as a novel therapeutic target.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome; Italy. barbara.rizzacasa@gmail.com.
Barbara
B
Rizzacasa
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome; Italy. morinielena.em@gmail.com.
Elena
E
Morini
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome; Italy. sabina.pucci@uniroma2.it.
Sabina
S
Pucci
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome; Italy. miky.murdi@hotmail.it.
Michela
M
Murdocca
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome; Italy. novelli@med.uniroma2.it.
Giuseppe
G
Novelli
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome; Italy. amati@med.uniroma2.it.
Francesca
F
Amati
D017398:Alternative Splicing; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D020033:Protein Isoforms; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
C495137:OLR1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E
OLR1; alternative splicing; atherosclerosis; cancer