Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer

Abstract

BackgroundPrevious studies identified microRNAs (miRNAs) and messenger RNAs with significantly different expression between normal pancreas and pancreatic cancer (PDAC) tissues. Due to technological limitations of microarrays and real-time PCR systems these studies focused on a fixed set of targets. Expression of other RNA classes such as long intergenic non-coding RNAs or sno-derived RNAs has rarely been examined in pancreatic cancer. Here, we analysed the coding and non-coding transcriptome of six PDAC and five control tissues using next-generation sequencing.ResultsBesides the confirmation of several deregulated mRNAs and miRNAs, miRNAs without previous implication in PDAC were detected: miR-802, miR-2114 or miR-561. SnoRNA-derived RNAs (e.g. sno-HBII-296B) and piR-017061, a piwi-interacting RNA, were found to be differentially expressed between PDAC and control tissues. In silico target analysis of miR-802 revealed potential binding sites in the 3′ UTR of TCF4, encoding a transcription factor that controls Wnt signalling genes. Overexpression of miR-802 in MiaPaCa pancreatic cancer cells reduced TCF4 protein levels. Using Massive Analysis of cDNA Ends (MACE) we identified differential expression of 43 lincRNAs, long intergenic non-coding RNAs, e.g. LINC00261 and LINC00152 as well as several natural antisense transcripts like HNF1A-AS1 and AFAP1-AS1. Differential expression was confirmed by qPCR on the mRNA/miRNA/lincRNA level and by immunohistochemistry on the protein level.ConclusionsHere, we report a novel lncRNA, sncRNA and mRNA signature of PDAC. In silico prediction of ncRNA targets allowed for assigning potential functions to differentially regulated RNAs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0358-5) contains supplementary material, which is available to authorized users.

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer

“…The expression of piR-015551 was positively correlated with the LNC00964-3 expression levels, indicating that piR-015551 may be possibly generated from LNC00964-3, which may be involved in the development of CRC. piR-017061, located within HBII-296A snoRNA, revealed to be dramatically down-regulated in pancreatic ductal adenocarcinoma (PDAC) compared to nonmalignant pancreatic control tissues [92]. Currently, Krishnan et al [93] discovered eight piRNAs as novel independent prognostic markers in breast cancer and their association with overall survival (OS) was confirmed in The Cancer Genome Atlas (TCGA) dataset.…”

tsRNA signatures in cancer

“…tsRNA | tRF | tDR | ncRNA | tRNA fragments I n the last decade, small noncoding RNAs (ncRNAs), including miRNAs and Piwi-interacting RNAs (piRNAs) (1)(2)(3), have been associated with cancer onset, progression, and drug response. Recently, a class of small ncRNAs was reported to derive from tRNA precursor or mature sequences, and their connection with cancer is currently under investigation (4).…”

Aberrant DNA hypermethylation-silenced SOX21-AS1 gene expression and its clinical importance in oral cancer

“…Among lncRNAs, lnc00152 has been reported to play an oncogenic role in promoting gastric cancer cell growth, migration, and invasion and in suppressing cell apoptosis by sponging miR-18a-5p, miR-195-3p, miR-139-5p, and miR-31-5p expression [23, 24]. In addition, lnc00152 was significantly overexpressed in pancreatic cancer [25]. However, in-depth biological function and the effect of dysfunctional lnc00152 on oral cancer remain unclear and require further investigation.…”