Long noncoding RNA FALEC inhibits proliferation and metastasis of tongue squamous cell carcinoma by epigenetically silencing ECM1 through EZH2.

Jianjiang Zhao,Bo Jia,Zhiping Wang,Xiaoling Qiu,Tao Xie,Zhijie Huang,Xianghuai Zheng,Jun Chen,Xiang Sun

doi:10.18632/aging.102094

Abstract

Tongue squamous cell carcinoma (TSCC), the most common epithelial cancer identified in the oral cavity, has become one of the most common malignancies across the developing countries. Increasing evidence indicates that long non-coding RNAs (lncRNAs) serve as important regulators in cancer biology. The focally amplified long non-coding RNA in epithelial cancer (FALEC) was found downregulated in the tissues of tongue squamous cell carcinoma (TSCC) and was predicted to present a good prognosis by bioinformatics analysis. Experiments indicated that FALEC knockdown significantly increased the proliferation and migration of TSCC cells both in vitro and in vivo; however, FALEC overexpression repressed these malignant behaviors. RNA pull-down and RNA immunoprecipitation demonstrated that FALEC could recruit enhancer of zeste homolog 2 (EZH2) at the promoter regions of extracellular matrix protein 1 (ECM1), epigenetically repressing ECM1 expression. The data revealed that FALEC acted as a tumor suppressor in TSCC and may aid in developing a novel potential therapeutic strategy against TSCC.

Highlights

Oral carcinoma, the most common epithelial cancer identified in the oral cavity, has become one of the most frequently occurring malignancies across the developing countries
FALEC is markedly decreased in tongue squamous cell carcinoma (TSCC) and predicts a good prognosis
In order to explore Long non-coding RNAs (lncRNAs) involved in the progression of TSCC, we analyzed the lncRNA expression profile in pre-therapy biopsies of TSCC samples and normal samples from the cancer Genome Atlas (TCGA) datasets

Summary

Introduction

The most common epithelial cancer identified in the oral cavity, has become one of the most frequently occurring malignancies across the developing countries. 25 to 40 % of oral squamous cells carcinomas were diagnosed as tongue squamous cells carcinomas (TSCC) [1,2,3]. Advances in surgery, chemotherapy, and radiotherapy, the prognosis of TSCC patients has not improved significantly over the past decades. It is critical to further understand the specific mechanism underlying the initiation and progression of TSCC. LncRNAs have been shown to play crucial roles in important biological processes, such as epigenetic regulation, genomic imprinting, X-chromatin remodeling, mRNA splicing and degradation, and regulation of gene expression [6]. LncRNAs can regulate gene expression and protein synthesis by cis-regulation (< 1 Mbps from the www.aging-us.com transcribed lncRNA) or trans-regulation (> 1 Mbps from transcribed lncRNA, even on other chromosomes)

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