Upregulated long non-coding RNA AFAP1-AS1 expression is associated with progression and poor prognosis of nasopharyngeal carcinoma.

Hao Bo,Qianjin Liao,Xiaoling Li,Jianbo Yang,Ke Tang,Wenling Zhang,Zheng Li,Ming Zhou,Bo Xiang,Yong Zeng,Yizhou Jing,Wei Xiong,Zhaojian Gong,Lei Shi,Guiyuan Li,Zhaoyang Zeng,Xiayu Li,Yanhong Zhou,Chaoyun Pan ,Li Yu

doi:10.18632/oncotarget.4057

Abstract

Altered expression of long noncoding RNAs (lncRNAs) associated with human carcinogenesis. We performed a cDNA microarray analysis of lncRNA expression in 12 cases of nasopharyngeal carcinoma (NPC) and 4 non-tumor nasopharyngeal epitheliums. One lncRNA, actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), was identified and selected for further study. AFAP1-AS1 expression was upregulated in NPC and associated with NPC metastasis and poor prognosis. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the NPC cell migration and invasive capability. AFAP1-AS1 knockdown also increased AFAP1 protein expression. Proteomic and bioinformatics analyses suggested that AFAP1-AS1 affected the expression of several small GTPase family members and molecules in the actin cytokeratin signaling pathway. AFAP1-AS1 promoted cancer cell metastasis via regulation of actin filament integrity. AFAP1-AS1 might be a potential novel marker that can predict cancer patient prognosis and as a potential therapeutic target for NPC.

Highlights

In Southeastern Asia, nasopharyngeal carcinoma (NPC) is a unique disease with significantly different risk factors, pathogenesis, clinical behaviors and treatment options than other head and neck cancers [1]
Based on NetAffx, Refseq and Ensembl noncoding RNA annotations, we identified 28 overlapping probe sets, representing 24 long noncoding RNAs (lncRNAs) that were differentially expressed in NPC when compared to normal nasopharyngeal epithelia
We first profiled the differential expression of genes in 12 NPC and 4 nasopharyngeal epithelial (NPE) tissue samples, and combined our data with a previously published Gene Expression Omnibus (GEO) dataset (GSE12452) [19] to identify differentially expressed lncRNAs in NPC

Summary

Introduction

In Southeastern Asia, nasopharyngeal carcinoma (NPC) is a unique disease with significantly different risk factors, pathogenesis, clinical behaviors and treatment options than other head and neck cancers [1]. Many genetic and epigenetic alterations in NPC have been reported [12]; the precise molecular mechanisms underlying NPC development and progression remain unclear. Long noncoding RNA (lncRNA) regulates gene transcription and post-transcriptional regulation and dysregulated LncRNA expression plays a crucial role in human carcinogenesis [13]. LncRNAs are non-protein-coding transcripts that are ≥ 200 nucleotides in length, and accumulating evidence indicates that they participate in many physiological processes by modulating gene expression at the epigenetic, transcriptional and posttranscriptional levels. Dysregulated lncRNA expression has been reported in a variety of human cancers, including nasopharyngeal carcinoma (NPC), lung, breast and colorectal cancers. LncRNAs appear to participate in all stages of cancer development, including tumor initiation, progression and metastasis. More than 50,000 lncRNAs have been reported in the human genome; the function of most of these lncRNAs remains unknown [13,14,15,16,17,18]

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Results

Conclusion