A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the epigenetic suppression of p27.

M Qiu,Y Zheng,D Feng,E Zhang,W Xia,R Yin,M Li,Y Xu,L Xu,J Wang,M Sun

doi:10.1038/cddis.2015.203

Abstract

Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers. However, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Here, we identified the expression profile of lncRNAs and protein-coding genes via microarrays analysis of paired LUAD tissues and adjacent non-tumor tissues from five female non-smokes with LUAD. A total of 498 lncRNAs and 1691 protein-coding genes were differentially expressed between LUAD tissues and paired adjacent normal tissues. A novel lncRNA, LUAD transcript 1 (LUADT1), which is highly expressed in LUAD and correlates with T stage, was characterized. Both in vitro and in vivo data showed that LUADT1 knockdown significantly inhibited proliferation of LUAD cells and induced cell cycle arrest at the G0–G1 phase. Further analysis indicated that LUADT1 may regulate cell cycle progression by epigenetically inhibiting the expression of p27. RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that LUADT1 binds to SUZ12, a core component of polycomb repressive complex 2, and mediates the trimethylation of H3K27 at the promoter region of p27. The negative correlation between LUADT1 and p27 expression was confirmed in LUAD tissue samples. These data suggested that a set of lncRNAs and protein-coding genes were differentially expressed in LUAD. LUADT1 is an oncogenic lncRNA that regulates LUAD progression, suggesting that dysregulated lncRNAs may serve as key regulatory factors in LUAD progression.

Highlights

Long noncoding RNA is a type of RNA molecules larger than 200 nucleotides that lacks protein-coding capacity.[5,6] Owing to their lack of reading frames, lncRNAs were originally considered as transcriptional noise
As an emerging paradigm of cancer research, many cancerspecific lncRNAs have been identified, a set of which have been validated as biomarkers for metastasis or prognosis, such as metastasis associated long antisense transcript 1 (MALAT-1),[13] HOX transcript antisense RNA (HOTAIR)[14] and colon cancer-associated transcript 2 (CCAT2)
We have focused on lncRNA and reported a lung adenocarcinoma (LUAD)-specific lncRNA, CCAT2 that is significantly upregulated in LUAD but not in lung squamous cell cancer (LSCC).[22]

Summary

Introduction

Long noncoding RNA (lncRNA) is a type of RNA molecules larger than 200 nucleotides that lacks protein-coding capacity.[5,6] Owing to their lack of reading frames, lncRNAs were originally considered as transcriptional noise. MALAT-1, as indicated by its name, is a lncRNA that is highly expressed in metastatic LUAD and associated with poor prognosis.[13,15] Currently, high-throughput technology such as RNA-sequencing and microarrays analysis has enable the characterization of lncRNA expression profile in biological processes[16,17,18] and diseases.[19,20,21]. Tel: +86 25 83284700; Fax: +86 25 83641062; Abbreviations: LUAD, lung adenocarcinoma; RIP, RNA immunoprecipitation; H3K27, histone 3 lysine 27; ChIP, chromatin immunoprecipitation; LUADT1, lung adenocarcinoma transcript 1; PRC2, polycomb repressive complex 2. Novel lncRNA, LUADT1 M Qiu et al the protein-coding genes and lncRNAs expression profile of LUAD in female non-smokers characterized by microarrays and the identification of a novel lncRNA LUAD transcript 1 (LUADT1). The silence of LUADT1 induced cell cycle arrest and significantly inhibited tumor growth both in vivo and in vitro

Methods

Results

Conclusion