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Comparison of Circulating miRNAs Expression Alterations in Matched Tissue and Plasma Samples During Colorectal Cancer Progression

  • Zsófia Brigitta Nagy
  • Barbara Kinga Barták
  • Alexandra Kalmár
  • Orsolya Galamb
  • Barnabás Wichmann
  • Magdolna Dank
  • Péter Igaz
  • Zsolt Tulassay
  • Béla Molnár
Original Article

Abstract

MicroRNAs (miRNAs) have been found to play a critical role in colorectal adenoma-carcinoma sequence. MiRNA-specific high-throughput arrays became available to detect promising miRNA expression alterations even in biological fluids, such as plasma samples, where miRNAs are stable. The purpose of this study was to identify circulating miRNAs showing altered expression between normal colonic (N), tubular adenoma (ADT), tubulovillous adenoma (ADTV) and colorectal cancer (CRC) matched plasma and tissue samples. Sixteen peripheral plasma and matched tissue biopsy samples (N n = 4; ADT n = 4; ADTV n = 4; CRC n = 4) were selected, and total RNA including miRNA fraction was isolated. MiRNAs from plasma samples were extracted using QIAamp Circulating Nucleic Acid Kit (Qiagen). Matched tissue-plasma miRNA microarray experiments were conducted by GeneChip® miRNA 3.0 Array (Affymetrix). RT-qPCR (microRNA Ready-to-use PCR Human Panel I + II; Exiqon) was used for validation. Characteristic miRNA expression alterations were observed in comparison of AD and CRC groups (miR-149*, miR-3196, miR-4687) in plasma samples. In the N vs. CRC comparison, significant overexpression of miR-612, miR-1296, miR-933, miR-937 and miR-1207 was detected by RT-PCR (p < 0.05). Similar expression pattern of these miRNAs were observed using microarray in tissue pairs, as well. Although miRNAs were also found in circulatory system in a lower concentration compared to tissues, expression patterns slightly overlapped between tissue and plasma samples. Detected circulating miRNA alterations may originate not only from the primer tumor but from other cell types including immune cells.

Keywords

microRNA Plasma Circulating microRNA Colorectal cancer Colorectal adenoma Microarray Real-time PCR Tissue 

Notes

Acknowledgments

This study was supported by the National Research, Development and Innovation Office (KMR-12-1-2012-0216 grant) and Hungarian Scientific Research Fund (OTKA-K111743) grant.

Compliance with Ethical Standards

All authors read and approved the final manuscript.

Conflict of Interest

The Authors declare that there is no conflict of interest.

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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Zsófia Brigitta Nagy
    • 1
  • Barbara Kinga Barták
    • 1
  • Alexandra Kalmár
    • 1
  • Orsolya Galamb
    • 1
    • 2
  • Barnabás Wichmann
    • 1
    • 2
  • Magdolna Dank
    • 3
  • Péter Igaz
    • 1
    • 2
  • Zsolt Tulassay
    • 1
    • 2
  • Béla Molnár
    • 1
    • 2
  1. 1.Molecular Gastroenterology Laboratory, 2nd Department of Internal MedicineSemmelweis UniversityBudapestHungary
  2. 2.Molecular Medicine Research GroupHungarian Academy of SciencesBudapestHungary
  3. 3.Department of Clinical OncologySemmelweis UniversityBudapestHungary

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