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Abstract
Despite years of research, we are still unraveling crucial stages of gene expression regulation in cancer. On the basis of major biological hallmarks, we hypothesized that there must be a uniform gene expression pattern and regulation across cancer types. Among non-coding genes, long non-coding RNAs (lncRNAs) are emerging as key gene regulators playing powerful roles in cancer. Using TCGA RNAseq data, we analyzed coding (mRNA) and non-coding (lncRNA) gene expression across 15 and 9 common cancer types, respectively. 70 significantly differentially expressed genes common to all 15 cancer types were enlisted. Correlating with protein expression levels from Human Protein Atlas, we observed 34 positively correlated gene sets which are enriched in gene expression, transcription from RNA Pol-II, regulation of transcription and mitotic cell cycle biological processes. Further, 24 lncRNAs were among common significantly differentially expressed non-coding genes. Using guilt-by-association method, we predicted lncRNAs to be involved in same biological processes. Combining RNA-RNA interaction prediction and transcription regulatory networks, we identified E2F1, FOXM1 and PVT1 regulatory path as recurring pan-cancer regulatory entity. PVT1 is predicted to interact with SYNE1 at 3′-UTR; DNAJC9, RNPS1 at 5′-UTR and ATXN2L, ALAD, FOXM1 and IRAK1 at CDS sites. The key findings are that through E2F1, FOXM1 and PVT1 regulatory axis and possible interactions with different coding genes, PVT1 may be playing a prominent role in pan-cancer development and progression.
Highlights
Cancer, a hitherto-largely impregnable disease, is characterized by distinct hallmarks (Hanahan & Weinberg, 2011) which generalize their biological complexity
Gene expression data was obtained from The Cancer Genome Atlas (TCGA) data portal
From the patterns observed from our plots, we identified that SNHG11, AC005154.5, MAGI2-AS3, MIR22HG, RP11-368I7.2, RP11-1149O23.3, and UHRF1 long non-coding RNAs (lncRNAs) interacted with KAT2B mRNA at 5 -UTR with higher SUMENERGY values except PVT1
Summary
A hitherto-largely impregnable disease, is characterized by distinct hallmarks (Hanahan & Weinberg, 2011) which generalize their biological complexity. Transformation of normal cells into abnormal ones, i.e., cancer, is associated with profound changes in gene expression profile (Kopnin, 2000; Ismail et al, 2000; Herceg & Hainaut, 2007). Factors and causes involved range from genetic (somatic mutation and copy number variations) to epigenetic changes which in turn, lead to differential gene expression due to dysregulation (Sadikovic, Al-Romaih & Squire J.A, 2008; Du & Che, 2017). Interacting with proteins and other RNAs, these may play an important role in signal transduction processes in cancer and normal cells in their capacity as signals, decoys, guides and scaffolds (Kung, Colognori & Lee, 2013). Many lncRNAs have been correlated with development and disease mainly due to the changes in their expression levels
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