Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression

Abstract

BackgroundNumerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown.MethodsQuantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24.ResultsLINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD.ConclusionsOur study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0581-3) contains supplementary material, which is available to authorized users.

The Long Intergenic Noncoding RNA 00707 Promotes Lung Adenocarcinoma Cell Proliferation and Migration by Regulating Cdc42

“…Particularly, a relationship between lncRNA and LAD has been suggested. LncRNA LINC00152 is upregulated remarkably in LAD, which promotes cell proliferation by binding to enhancer of zeste homology 2 and repressing the expression of interleukin 24 [16]. LncRNA CCAT1 is responsible for the chemoresistance of docetaxel-resistant LAD cells through sponging let-7c and releasing Bcl-xl [17].…”

Systematic identification of lincRNA‐based prognostic biomarkers by integrating lincRNA expression and copy number variation in lung adenocarcinoma

“…showed that TDRKH‐AS1 expression significantly correlated with the enhancer of zeste homolog 2 (EZH2) expression . TDRKH‐AS1 may be involved in the epigenetic silencing of gene expression by recruiting EZH2, such as CDKN1A, CDKN1B and IL24 . Furthermore, its copy number is altered in 13.16% of the LUAD patients.…”

Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16

“…Chen et al recently reported that LINC00152 is upregulated in lung adenocarcinoma and is associated with a poor prognosis. Meanwhile, LINC00152’s oncogenic effects are mediated in part by the epigenetic silencing of IL24 expression after binding to EZH2 [9]. In the present study, we determined the expression pattern of LINC00152 in several glioma cell lines and in the normal human astrocytes NHAs using qRT–PCR.…”

“…The small interfering RNAs (siRNAs) targeting LINC00152 (siLINC00152_1 and siLINC00152_2) were synthesized by Genepharma (Shanghai, China) [9]. LINC00152 short hairpin RNA (shRNA) was cloned into the pLKO.1 vector, and lentiviral particle production was performed according to a previous report [11].…”