Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

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62 Citations (Scopus)

Abstract

Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.

Original languageEnglish
Pages (from-to)36366-36381
Number of pages16
JournalOncotarget
Volume7
Issue number24
DOIs
Publication statusPublished - 2016

Fingerprint

Carcinoma
Ovarian Neoplasms
Messenger RNA
Neoplasms
RNA
Neoplasm Metastasis
RNA Sequence Analysis
MicroRNAs
Transcriptome
Libraries
Mammals
Seeds
Protein Isoforms
Biomarkers
Lymph Nodes
Gene Expression
circular RNA
Therapeutics

Keywords

  • Circular RNA
  • Lymph node metastasis
  • MiRNA
  • Ovarian cancer
  • Peritoneal metastasis

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma",
abstract = "Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.",
keywords = "Circular RNA, Lymph node metastasis, MiRNA, Ovarian cancer, Peritoneal metastasis",
author = "Ikhlak Ahmed and {Karedath Abdul Azis}, Thasni and Andrews, {Simeon S.} and {Al Azwani}, Iman and {Ali Mohamoud}, Yasmin and Denis Querleu and Tabrizi, {Arash Rafii} and Joel Malek",
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T1 - Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

AU - Ahmed, Ikhlak

AU - Karedath Abdul Azis, Thasni

AU - Andrews, Simeon S.

AU - Al Azwani, Iman

AU - Ali Mohamoud, Yasmin

AU - Querleu, Denis

AU - Tabrizi, Arash Rafii

AU - Malek, Joel

PY - 2016

Y1 - 2016

N2 - Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.

AB - Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.

KW - Circular RNA

KW - Lymph node metastasis

KW - MiRNA

KW - Ovarian cancer

KW - Peritoneal metastasis

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