Journal Article

Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma

Zhi, Kangkang, Bi, Jianwei, Fang, Guoen, Gu, Yan, Yang, Feng, Xue, Xuchao, Zheng, Luming

2013

Overview

Purpose Long noncoding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are deregulated in many tumors. The specific aim of this study was to determine the role of a long noncoding RNA CCAT1 in the progression of gastric carcinoma and discover which factors contribute to the deregulation of CCAT1. Methods A computational screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with the CCAT1 promoter in vivo was tested by chromatin immunoprecipitation assay. CCAT1 promoter activities were examined by luciferase reporter assay. The function of the c-Myc binding site in the CCAT1 promoter region was tested by a promoter assay with nucleotide substitutions in the putative E-box. The effect of CCAT1 on gastric carcinoma cell proliferation and migration was tested using in vitro cell proliferation and migration assays. Results CCAT1 levels were markedly increased in gastric carcinoma tissues compared with normal tissues. c-Myc directly binds to the E-box element in the promoter region of CCAT1 , and when ectopically expressed increased promoter activity and expression of CCAT1. Nucleotide substitutions in the E-box element in the promoter region abrogated c-Myc-dependent promoter activation. The expression of CCAT1 and c-Myc shows strong association in gastric carcinomas. Moreover, abnormally expressed CCAT1 promotes cell proliferation and migration. Conclusions These data suggest that c-Myc induction of CCAT1 holds an important role in gastric carcinoma and implicate the potential application of CCAT1 in the treatment of gastric carcinoma.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Antineoplastic agents / Biological and medical sciences / c-Myc protein / Cancer Research / Carcinoma - genetics / Carcinoma - pathology / Case-Control Studies / Cell migration / Cell proliferation / Chromatin / Computer applications / Data processing / Disease Progression / Gastric cancer / Gastroenterology. Liver. Pancreas. Abdomen / Gene Expression Regulation, Neoplastic - drug effects / Gene Expression Regulation, Neoplastic - physiology / Hematology / Humans / Immunoprecipitation / Internal Medicine / Medical sciences / Medicine / Medicine & Public Health / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Nucleotides / Oncology / Original Paper / Pharmacology. Drug treatments / Promoter Regions, Genetic / Promoters / Protein Binding / Proto-Oncogene Proteins c-myc - antagonists & inhibitors / Proto-Oncogene Proteins c-myc - genetics / Proto-Oncogene Proteins c-myc - metabolism / Proto-Oncogene Proteins c-myc - physiology / Ribonucleic acid / RNA / RNA, Long Noncoding - antagonists & inhibitors / RNA, Long Noncoding - genetics / RNA, Long Noncoding - physiology / RNA, Small Interfering - pharmacology / Stomach Neoplasms - genetics / Stomach Neoplasms - pathology / Stomach. Duodenum. Small intestine. Colon. Rectum. Anus / Transcription / Transcriptional Activation - genetics / Transcriptional Activation - physiology / Transfection / Tumor Cells, Cultured / Tumors