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Identification of novel dysregulated circular RNAs in early-stage breast cancer
Authors:Arunagiri Kuha Deva Magendhra Rao  Vittal Rangan Arvinden  Deepa Ramasamy  Krishna Patel  Balaiah Meenakumari  Priya Ramanathan  Shirley Sundersingh  Velusami Sridevi  Thangarajan Rajkumar  Zdenko Herceg  Harsha Gowda  Samson Mani
Institution:1. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Conceptualization (lead), Formal analysis (lead), ?Investigation (lead), Methodology (lead), Validation (lead), Visualization (lead), Writing - original draft (lead);2. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Formal analysis (equal), Methodology (equal), Visualization (equal);3. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Formal analysis (supporting);4. Institute of Bioinformatics, ITPL, Bangalore, India

Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India

Contribution: Formal analysis (supporting);5. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Methodology (supporting);6. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Writing - review & editing (supporting);7. Department of Oncopathology, Cancer Institute (WIA), Chennai, India

Contribution: Resources (lead);8. Department of Surgical Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Resources (lead);9. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Contribution: Supervision (supporting), Writing - review & editing (supporting);10. Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France

Contribution: Writing - review & editing (supporting);11. Institute of Bioinformatics, ITPL, Bangalore, India

Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India

Manipal Academy of Higher Education (MAHE), Manipal, India

QIMR Berghofer, Royal Brisbane Hospital QLD, Brisbane, Qld, Australia

Contribution: Formal analysis (supporting);12. Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India

Abstract:Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early-stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circRNA-miRNA (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA-miRNA interaction which could be involved in breast cancer development.
Keywords:breast cancer  circRNA as microRNA precursor  circRNA-microRNA interaction  circular RNA  non-coding RNA
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