Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer

Abstract

BackgroundLong intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive.ResultsHere we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation.ConclusionsOur systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0429-8) contains supplementary material, which is available to authorized users.

Comprehensive discovery of noncoding RNAs in acute myeloid leukemia cell transcriptomes

“…Using a previously described method 18 to comprehensively annotate lncRNAs in AML31 we identified 977 previously unannotated multi-exon lncRNA transcripts (See Table S5 for details). The expression levels of the multi-exon lncRNAs are shown in Figure 4A, which combine the datasets for AML31 and the TCGA AML cohort.…”

“…AML31 RNA-seq samples were used to discover novel expressed transcripts using the same methods in 18 . Sequencing reads were aligned using TopHat2 42 .…”

“…However, despite the annotation of thousands of lncRNAs in human development and cancer, only a minor subset is well characterized in the context of leukemia. Furthermore, previous developmental 14,15 and cancer transcriptome studies 2,16–18 have revealed highly specific expression profiles for lncRNAs, suggesting that the full spectrum of biologically and clinically relevant lncRNAs may be under-represented in leukemia datasets. However, a major challenge is determining the necessary amount of sequencing needed to detect the full spectrum, due to the variable read coverage across transcript types with highly variable expression levels 19 .…”

The Emerging Role and Promise of Long Noncoding RNAs in Lung Cancer Treatment

“…Functional validation shows that the most differentially expressed lncRNA across lung subtypes, LCAL1 (lung cancer associated lncRNA 1), contributes to cellular proliferation [46]. Furthermore, siRNA-mediated knockdown of MVIH could inhibit cell growth via regulating MMP-2 and MMP-9 protein expression in NSCLC [47].…”

LncRNAs in vertebrates: Advances and challenges

“…In addition, analysis of over 300 additional tumor types identified both lung cancer-specific lncRNAs as well as a subset of lncRNAs that are broadly deregulated in many human cancers [51]. Furthermore, Tseng and co-authors surveyed the Cancer Genome Atlas database, representing more than 15,000 tumors, and showed that 18% of these tumors showed a gain in copy-number of the PVT1-containing 8q24.21 region and that nearly 100% of this subpopulation also showed a MYC copy number increase [47].…”