Comparison of Circulating miRNAs Expression Alterations in Matched Tissue and Plasma Samples During Colorectal Cancer Progression
- 169 Downloads
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.
KeywordsmicroRNA Plasma Circulating microRNA Colorectal cancer Colorectal adenoma Microarray Real-time PCR Tissue
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.
- 2.Patai AV, Valcz G, Hollosi P, Kalmar A, Peterfia B, Patai A, Wichmann B, Spisak S, Bartak BK, Leiszter K, Toth K, Sipos F, Kovalszky I, Peter Z, Miheller P, Tulassay Z, Molnar B (2015) Comprehensive DNA methylation analysis reveals a common ten-gene methylation signature in colorectal adenomas and carcinomas. PLoS One 10(8):e0133836. https://doi.org/10.1371/journal.pone.0133836 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Nagy ZB, Wichmann B, Kalmar A, Galamb O, Bartak BK, Spisak S, Tulassay Z, Molnar B (2017) Colorectal adenoma and carcinoma specific miRNA profiles in biopsy and their expression in plasma specimens. Clin Epigenetics 9:22. https://doi.org/10.1186/s13148-016-0305-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. P Natl Acad Sci USA 105(30):10513–10518. https://doi.org/10.1073/pnas.0804549105 CrossRefGoogle Scholar
- 12.Pathak S, Meng WJ, Nandy SK, Ping J, Bisgin A, Helmfors L, Waldmann P, Sun XF (2015) Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner. Oncotarget 6(42):44758–44780. https://doi.org/10.18632/oncotarget.5815 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Zhou N, Zhou Y, Tang Y, Yu W (2016) MiR-519 inhibits gastric cancer cell activity through regulation of HuR expression. Journal of Central South University Medical Sciences 41(1):19–23. https://doi.org/10.11817/j.issn.1672-7347.2016.01.003 PubMedGoogle Scholar
- 16.Bhajun R, Guyon L, Pitaval A, Sulpice E, Combe S, Obeid P, Haguet V, Ghorbel I, Lajaunie C, Gidrol X (2015) A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator. Sci Rep 5:8336. https://doi.org/10.1038/Srep08336 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Bobowicz M, Skrzypski M, Czapiewski P, Marczyk M, Maciejewska A, Jankowski M, Szulgo-Paczkowska A, Zegarski W, Pawlowski R, Polanska J, Biernat W, Jaskiewicz J, Jassem J (2016) Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer. Clin Exp Metastasis 33(8):765–773. https://doi.org/10.1007/s10585-016-9810-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Cakmak HA, Coskunpinar E, Ikitimur B, Barman HA, Karadag B, Tiryakioglu NO, Kahraman K, Vural VA (2015) The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med 16(6):431–437. https://doi.org/10.2459/JCM.0000000000000233 CrossRefGoogle Scholar
- 19.Shan X, Wen W, Zhu D, Yan T, Cheng W, Huang Z, Zhang L, Zhang H, Wang T, Zhu W, Zhu Y, Zhu J (2017) miR 1296-5p inhibits the migration and invasion of gastric cancer cells by repressing ERBB2 expression. PLoS One 12(1):e0170298. https://doi.org/10.1371/journal.pone.0170298 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Wei WJ, Wang YL, Li DS, Wang Y, Wang XF, Zhu YX, Pan XD, Wang ZY, Wu Y, Jin L, Wang JC, Ji QH (2015) Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population. Endocrine 49(2):436–444. https://doi.org/10.1007/s12020-014-0467-8 CrossRefPubMedGoogle Scholar
- 22.Poliseno L, Haimovic A, Segura MF, Hanniford D, Christos PJ, Darvishian F, Wang J, Shapiro RL, Pavlick AC, Berman RS, Hernando E, Zavadil J, Osman I (2012) Histology-specific microRNA alterations in melanoma. J Invest Dermatol 132(7):1860–1868. https://doi.org/10.1038/jid.2011.451 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Wang W, Sun J, Li F, Li R, Gu Y, Liu C, Yang P, Zhu M, Chen L, Tian W, Zhou H, Mao Y, Zhang L, Jiang J, Wu C, Hua D, Chen W, Lu B, Ju J, Zhang X (2012) A frequent somatic mutation in CD274 3′-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding. Hum Mutat 33(3):480–484. https://doi.org/10.1002/humu.22014 CrossRefPubMedGoogle Scholar
- 28.Ali Sheikh MS, Xia K, Li F, Deng X, Salma U, Deng H, Wei Wei L, Yang TL, Peng J (2015) Circulating miR-765 and miR-149: potential noninvasive diagnostic biomarkers for geriatric coronary artery disease patients. Biomed Res Int 2015:740301. https://doi.org/10.1155/2015/740301 CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Larrea E, Sole C, Manterola L, Goicoechea I, Armesto M, Arestin M, Caffarel MM, Araujo AM, Araiz M, Fernandez-Mercado M, Lawrie CH (2016) New concepts in cancer biomarkers: circulating miRNAs in liquid biopsies. Int J Mol Sci 17(5):627. https://doi.org/10.3390/ijms17050627 CrossRefPubMedCentralGoogle Scholar