Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

Hassel, Jessica C.; Amann, Philipp M.; Schadendorf, Dirk; Eichmüller, Stefan B.; Nagler, Markus; Bazhin, Alexandr V.

doi:10.1111/exd.12236

Cited by 11 publications

(10 citation statements)

References 20 publications

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“…Interestingly, patients with LRAT hypermethylation did present a favorable prognosis (p = 0.03). Consistent with our finding, a recent study has also demonstrated high expression of LRAT in melanoma metastases was inversely correlated with patient survival [12]. Our data suggest that the frequent LRAT hypermethylation may represent a useful predictor to stratify CRC.…”

Section: Resultssupporting

confidence: 92%

LRAT Promoter Hypermethylation as a Prognostic Marker for Colorectal Cancer Impairs Retinol Metabolism

DePaoli¹,

Barany²,

Cheng³

2017

J Clin Gastroenterol Treat

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Retinoids and its derivatives are known to regulate tumor progression. Our previous study in Colorectal Cancer (CRC) has shown that the expression of LRAT, a gene converts excess retinol into retinyl ester to balance retinoids homeostasis, may be regulated by its promoter methylation status to modulate the retinoids synthesis. In this report, we begin to explore the potential mechanism of LRAT mediated retinoid metabolism. Our data indicate CRC patient of LRAT hypermethylation associated with better prognosis. A consistent finding is shown in siRNA mediated LRAT silencing, which leads to slow growth of CRC cell lines. We have also observed favorable CRC prognosis occurred in patients of both LRAT and RAR-beta hypermethylation, suggesting the better CRC prognosis may be mediated through RAR beta independent pathway.

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Section: Resultssupporting

confidence: 92%

LRAT Promoter Hypermethylation as a Prognostic Marker for Colorectal Cancer Impairs Retinol Metabolism

DePaoli¹,

Barany²,

Cheng³

2017

J Clin Gastroenterol Treat

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“…The drop in LRAT expression is also consistent with previous findings of reduced retinyl esters with UVA and UVB exposure and reduced LRAT expression and activity in SCC . It has been argued that a decrease in retinyl esters may contribute to retinoid deficiency in cancer cells, and LRAT expression may reduce cancer cell survival . But by also showing that RA synthesis enzymes and binding proteins are increased we paint a different picture.…”

Section: Discussionsupporting

confidence: 88%

Endogenous Retinoic Acid Required to Maintain the Epidermis Following Ultraviolet Light Exposure in SKH‐1 Hairless Mice

Gressel

Duncan

Oberyszyn

et al. 2015

Photochem & Photobiology

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Ultraviolet light B (UVB) exposure induces cutaneous squamous cell carcinoma (cSCC), one of the most prevalent human cancers. Reoccurrence of cSCC in high-risk patients is prevented by oral retinoids. But oral retinoid treatment causes significant side effects; and patients develop retinoid resistance. Exactly how retinoids prevent UVB-induced cSCC is currently not well understood. Retinoid resistance blocks mechanistic studies in the leading mouse model of cSCC, the UVB exposed SKH-1 hairless mouse. To begin to understand the role of retinoids in UVB-induced cSCC we first examined the localization pattern of key retinoid metabolism proteins by immunohistochemistry 48 hours after UVB treatment of female SKH-1 mice. We next inhibited retinoic acid (RA) synthesis immediately after UVB exposure. Acute UVB increased RA synthesis, signaling, and degradation proteins in the stratum granulosum. Some of these proteins changed their localization; while other proteins just increased in intensity. In contrast, acute UVB reduced the retinoid storage protein lectin:retinol acyltransferase (LRAT) in the epidermis. Inhibiting RA synthesis disrupted the epidermis and impaired differentiation. These data suggests that repair of the epidermis after acute UVB exposure requires endogenous RA synthesis.

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“…Moreover, lecithin retinol acyltransferase (LRAT) is a major enzyme involved in vitamin A metabolism by catalysing the esterification of all-trans-retinol into all-trans-retinyl ester, which regulates various physiological processes. However, it is frequently inhibited by promoter hypermethylation in numerous cancers 40 41 42 . In this study, we showed that the LRAT promoter (GRCh37/Hg19 chr4: 155663541–155664999) was hypermethylated in six IUGR placental shares and the inter-group comparisons displayed a similar result ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns

Luo

et al. 2016

Sci Rep

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Intrauterine growth restriction (IUGR) affects the foetus and has a number of pathological consequences throughout life. Recent work has indicated that variations in DNA methylation might cause placental dysfunction, which may be associated with adverse pregnancy complications. Here, we investigated the promoter methylomes of placental shares from seven monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR) using the healthy twin as an ideal control. Our work demonstrated that the IUGR placental shares harboured a distinct DNA hypomethylation pattern and that the methylation variations preferentially occurred in CpG island shores or non-CpG island promoters. The differentially methylated promoters could significantly separate the IUGR placental shares from the healthy ones. Ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) further confirmed the genome‐wide DNA hypomethylation and the lower level of hydroxymethylation statuses in the IUGR placental shares. The methylation variations of the LRAT and SLC19A1 promoters, which are involved in vitamin A metabolism and folate transportation, respectively, and the EFS promoter were further validated in an additional 12 pairs of MC twins with sIUGR. Although the expressions of LRAT, SLC19A1 and EFS were not affected, we still speculated that DNA methylation and hydroxymethylation might serve a functional role during in utero foetal development.

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Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

Cited by 11 publications

References 20 publications

LRAT Promoter Hypermethylation as a Prognostic Marker for Colorectal Cancer Impairs Retinol Metabolism

LRAT Promoter Hypermethylation as a Prognostic Marker for Colorectal Cancer Impairs Retinol Metabolism

Endogenous Retinoic Acid Required to Maintain the Epidermis Following Ultraviolet Light Exposure in SKH‐1 Hairless Mice

The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns

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