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Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.

ABSTRACT: The functions and biomarker potential of circular RNAs (circRNAs) in various cancer types are a rising field of study, as emerging evidence relates circRNAs to tumorigenesis. Here, we profiled the expression of circRNAs in 457 tumors from patients with non-muscle-invasive bladder cancer (NMIBC). We show that a set of highly expressed circRNAs have conserved core splice sites, are associated with Alu repeats, and enriched with Synonymous Constraint Elements as well as microRNA target sites. We identified 113 abundant circRNAs that are differentially expressed between high and low-risk tumor subtypes. Analysis of progression-free survival revealed 13 circRNAs, among them circHIPK3 and circCDYL, where expression correlated with progression independently of the linear transcript and the host gene. In summary, our results demonstrate that abundant circRNAs possess multiple biological features, distinguishing them from low-expressed circRNAs and non-circularized exons, and suggest that circRNAs might serve as a new class of prognostic biomarkers in NMIBC.

SUBMITTER: Okholm TLH

PROVIDER: S-EPMC5705701 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.

Okholm Trine Line Hauge TLH Nielsen Morten Muhlig MM Hamilton Mark P MP Christensen Lise-Lotte LL Vang Søren S Hedegaard Jakob J Hansen Thomas Birkballe TB Kjems Jørgen J Dyrskjøt Lars L Pedersen Jakob Skou JS

NPJ genomic medicine 20171128

The functions and biomarker potential of circular RNAs (circRNAs) in various cancer types are a rising field of study, as emerging evidence relates circRNAs to tumorigenesis. Here, we profiled the expression of circRNAs in 457 tumors from patients with non-muscle-invasive bladder cancer (NMIBC). We show that a set of highly expressed circRNAs have conserved core splice sites, are associated with Alu repeats, and enriched with Synonymous Constraint Elements as well as microRNA target sites. We id ...[more]

PMID: 29263845

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Project description:BackgroundThe pathogenesis and developmental mechanism of early-stage (FIGO 2009 IA2-IIA2) cervical cancer (CC) remain unclear. Seeking novel molecular biomarkers based on The Cancer Genome Atlas (TCGA) will facilitate the understanding of CC pathogenesis and help evaluate early-stage CC prognosis.MethodsTo identify prognosis-related genes in early-stage CC, we analyzed TCGA mRNA-seq data and clinical data by univariate Cox and Kaplan-Meier plotter analyses. Differential expression analysis identified upregulated genes in early-stage CC. Combined with the genes correlated with unfavorable prognosis, we selected desmoglein-2 (DSG2) for further investigation. To detect DSG2 expression in early-stage CC, we used immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blotting. The relationship between the expression of DSG2 and clinical features was analyzed by the Chi square test. Cox analysis was applied to assess the relationship between CC overall survival (OS) and risk factors. The correlations between DSG2 expression and CC cell line proliferation and migration were investigated with Cell Counting Kit-8 (CCK-8) and migration assays.ResultsThere were 416 prognosis-related genes in early-stage CC. DSG2, matrix metallopeptidase 1 (MMP1), carbonic anhydrase IX (CA9), homeobox A1 (HOXA1), and serine protease inhibitor B3 (SERPINB3) were upregulated in early-stage CC compared with adjacent noncancerous tissue (ANT) and correlated with unfavorable prognosis. Among them, DSG2 was most significantly correlated with patient survival. Coexpression analysis indicated that DSG2 was probably involved in cell division, positive regulation of transferase activity, positive regulation of cell migration, EGFR upregulation pathway and regulation of lymphangiogenesis. IHC, qRT-PCR and western blotting showed that DSG2 expression was higher in CC than in normal tissue. Significant correlations were identified between DSG2 expression and several aggressive clinical features, including pelvic lymph node metastasis (PLNM). Multivariate Cox analysis showed that DSG2 and PLNM were independent prognostic factors for OS. DSG2 knockdown inhibited CC cell proliferation and migration.ConclusionsDSG2 is a biomarker that promotes tumor proliferation and metastasis and is correlated with poor prognosis in early-stage CC.

Dataset Information

Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.

Publications

Circular RNA expression is abundant and correlated to aggressiveness in early-stage bladder cancer.

Similar Datasets

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