Abstract

// Yu Mao 1 , Lixin Dong 1 , Jia Liu 2 , Liang Li 3 , Le Wang 4 , Yan Zhou 5 , Yanqiu Zhang 1 , Sen Yang 1 , Liyan Cao 1 , Chao Wang 6 and Zhanzhao Fu 1 1 Department of Oncology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China 2 Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, China 3 Department of Ultrasound, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 4 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute and Laboratory of Neuro-Oncology, Tianjin, China 5 Department of Oncology Radiation, Tianjin Medical University General Hospital, Tianjin, China 6 Department of Thoracic Surgery, The First Hospital of Qinhuangdao, Qinhuangdao, China Correspondence to: Zhanzhao Fu, email: doctors12email@163.com Keywords: ESCC; progression; long non-coding RNA; CCAT1 Received: February 27, 2017 Accepted: August 23, 2017 Published: January 02, 2018 ABSTRACT Dysregulation of long non-coding RNA (lncRNAs) plays vital roles in tumorigenesis and cancer progression. Previous studies have identified the role of the lncRNA CCAT1 as an oncogene in several cancer types, and ectopic expression of CCAT1 predicts a poor prognosis. This study sought to determine the underlying mechanism for this observation in esophageal squamous cell carcinoma (ESCC). We found that CCAT1 was significantly upregulated in human ESCC tumor tissues and cell lines. LncRNA CCAT1 overexpression enhanced cell proliferation, migration, and invasion in vitro and in vivo . Our bioinformatics analysis and RNA immunoprecipitation assays combined with dual-luciferase assays revealed that CCAT1 functions as a microRNA (miRNA) sponge for miR-543. Increased CCAT1 antagonized the functions of miRNA-543 and led to de-repression of its downstream target, KRAS, which is a core oncogene that facilitates ESCC progression. Our findings suggest that CCAT1 increases KRAS expression by sponging miR-543 and thus promotes ESCC progression. This study sheds light on the potential role of lncRNAs as a novel prognostic biomarker and provides a new therapeutic target for ESCC.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common primary malignancy and the third leading cause of cancer-related death [1]

  • After adjustment for age, gender, smoking status, drinking status, HBsAg status, and family history of cancers, three H19 polymorphisms were not associated with hepatocellular carcinoma (HCC) risk under any genetic models

  • The odds ratio (OR) per risk allele for HCC was 1.03 (95% confidence interval [95% CI] = 0.94–1.13) for rs2839702, 1.05 for rs2067051, and 1.04 for rs2075745, respectively

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common primary malignancy and the third leading cause of cancer-related death [1]. The treatment of HCC has made great advance, the long-term survival still remains quite low, with the 5 year survival rate of 22% [2]. Elucidation of the etiological factors for the development of HCC would be of great help to develop the effectively preventative and therapeutic approaches for HCC. Genetic basis could predispose to the HCC development and explain why only a fraction of individuals develop HCC when exposed to the same risk environment. Overexpression of H19 long non-coding RNA (lncRNA) has been observed in hepatocellular carcinoma (HCC), the role of H19 polymorphisms in the development of HCC was still unclear. In this study, we aimed to explore whether the H19 polymorphisms were related to the susceptibility of HCC

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