A lot of long non-coding RNAs (lncRNAs) are expressed in human cells in a number of transcripts of different lengths and composition of exons. In case of cancer-associated lncRNAs, an actual task is to determine their specific isoforms, since each transcript can perform its own function in carcinogenesis and might have a unique expression profile in various types of tumors. For the first time, we analyzed the expression of CASC8 lncRNA in human pancreatic ductal adenocarcinoma cell lines and found an abundant isoform that was previously considered as the minor one in this type of cancer. We also revealed extremely high expression levels of all CASC8 transcripts in MIA PaCa-2 cells and, conversely, the lack of this lncRNA in PANC-1. This allows to use them as convenient models for further in vitro studies.
SUMMARYProstate adenocarcinoma (PRAD) is the second most common cause of cancer-related deaths in men. In PRAD, high variability in DNA methylation and a high rate of large genomic rearrangements is often observed. To elucidate the reasons behind such high variance, we integrated DNA methylation, RNA-seq, and copy number alterations datasets from The Cancer Genome Atlas (TCGA) focusing on PRAD and subsequently employed weighted gene co-expression network analysis (WGCNA). Results from the studies show that only a single cluster of co-expressed genes is associated with genomic and epigenomic instability. Within this cluster, TP63 and TRIM29 are regulators and were both downregulated in PRAD. We show that TP63 regulates the level of enhancer methylation in prostate basal epithelium cells. TRIM29 forms a complex with TP63 and together regulate the expression of genes specific to the prostate basal epithelium. Moreover, TRIM29 binds DNA repair proteins and prevents the formation of the TMPRSS2:ERG gene fusion typically seen in PRAD. Therefore, the study shows that TRIM29 and TP63 are important regulators maintaining the identity of the basal epithelium. Finally, we uncover the role of TRIM29 in genome protection functions in PRAD.HIGHLIGHTSIdentification of clusters of co-expressed genes associated with epigenomic variability and chromosomal instability in prostate adenocarcinomaTP63 and TRIM29 together regulate the expression of the cluster genesTP63 regulates methylation of enhancers associated with the clusterTRIM29 decreases chromosomal instability in prostate adenocarcinoma
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