The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma

Jung Ho Yoon, Bo Hyun You, Chan Hyuk Park, Yeong Jin Kim, Jin Wu Nam, Sang Kil Lee

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.

Original languageEnglish
Pages (from-to)47-57
Number of pages11
JournalCancer Letters
Volume417
DOIs
Publication statusPublished - 2018 Mar 28

Fingerprint

Long Noncoding RNA
Ubiquitination
Methyltransferases
Carcinogenesis
DNA
DNA Methylation
Protein Methyltransferases
Neoplasms
Tumor Suppressor Genes
Epigenomics
Small Interfering RNA
Lung Neoplasms
Survival Rate
Biomarkers
Cell Proliferation
Esophageal Squamous Cell Carcinoma
Apoptosis
Neoplasm Metastasis
Cell Line
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{fa74bc2fa06f47e7854195a9ae4f00b2,
title = "The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma",
abstract = "Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.",
author = "Yoon, {Jung Ho} and You, {Bo Hyun} and Park, {Chan Hyuk} and Kim, {Yeong Jin} and Nam, {Jin Wu} and Lee, {Sang Kil}",
year = "2018",
month = "3",
day = "28",
doi = "10.1016/j.canlet.2017.12.016",
language = "English",
volume = "417",
pages = "47--57",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",

}

The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma. / Yoon, Jung Ho; You, Bo Hyun; Park, Chan Hyuk; Kim, Yeong Jin; Nam, Jin Wu; Lee, Sang Kil.

In: Cancer Letters, Vol. 417, 28.03.2018, p. 47-57.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma

AU - Yoon, Jung Ho

AU - You, Bo Hyun

AU - Park, Chan Hyuk

AU - Kim, Yeong Jin

AU - Nam, Jin Wu

AU - Lee, Sang Kil

PY - 2018/3/28

Y1 - 2018/3/28

N2 - Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.

AB - Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.

UR - http://www.scopus.com/inward/record.url?scp=85039956757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039956757&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2017.12.016

DO - 10.1016/j.canlet.2017.12.016

M3 - Article

C2 - 29247823

AN - SCOPUS:85039956757

VL - 417

SP - 47

EP - 57

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

ER -