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LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer

 Hyo Joo Byun  ;  Jung Ho Yoon  ;  Sang Kil Lee 
 YONSEI MEDICAL JOURNAL, Vol.61(11) : 923-934, 2020-11 
Journal Title
Issue Date
Apoptosis / genetics ; Biomarkers, Tumor / genetics ; Cell Proliferation / genetics ; Cell Survival ; DNA-Binding Proteins / genetics* ; DNA-Binding Proteins / metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic / genetics ; Genes, Tumor Suppressor* ; Humans ; Lung Neoplasms / genetics ; Membrane Proteins / genetics* ; Membrane Proteins / metabolism ; Neoplasm Invasiveness / genetics* ; RNA, Long Noncoding / genetics ; RNA, Long Noncoding / metabolism* ; RNA, Small Interfering / metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms / genetics* ; Stomach Neoplasms / pathology ; Transcription Factors / genetics* ; Transcription Factors / metabolism ; Up-Regulation ; Wnt Signaling Pathway
LUCAT1 ; Long non-coding RNA ; epigenetic modulation ; gastric cancer
Purpose: The mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC. Materials and methods: The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1). Results: LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (p<0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (p<0.05), and these reductions were restored by pcDNA-LUCAT1 (p<0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2. The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2. Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/β-catenin signaling pathway. Conclusion: We concluded that LUCAT1 induces methylation of CXXC4 and SFRP2, thereby regulating Wnt/β-catenin signaling in GC.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
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