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 journalArticlepeer-review

91 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

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by Korea government (Ministry of Science and ICT(No. NRF-2017R1A2B4006316 ), the Brain Korea 21 PLUS Project for Medical Science, Yonsei University and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute with funding from Ministry of Health and Welfare (grant number: HI15C1578 ). The results shown here are in part based upon data generated by TCGA, FANTOM consortia, and GTEx Projects.

Publisher Copyright:
© 2017 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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