Elevated microRNA expression could be diagnostic biomarker for PDAC

Mortoglou, M., Arisan, D., Ferreira, T., McCormick, A.L. and Uysal Onganer, P. 2020. Elevated microRNA expression could be diagnostic biomarker for PDAC. Pancreatology. 20 (8) e19. https://doi.org/10.1016/j.pan.2020.10.015

TitleElevated microRNA expression could be diagnostic biomarker for PDAC
TypeJournal article
AuthorsMortoglou, M., Arisan, D., Ferreira, T., McCormick, A.L. and Uysal Onganer, P.
Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of PCa with 2-9% 5-year survival rate. PDAC is the most lethal malignancy worldwide and hence the molecular mechanisms, which are linked to the aggressive features, should be further examined to develop better diagnostic, prognostic and therapeutic agents. microRNAs (miRs) are small non-coding RNAs (18–24 nucleotides), that can control cell growth, proliferation, apoptosis, differentiation, metastasis and angiogenesis. Furthermore, several studies have suggested that miRs could be utilized for the discrimination between PDAC and non-malignant lesions and thus the evaluation of them as novel diagnostic biomarkers is crucial for PDAC. Aim of this study is to examine miRs and their role in PDAC progression and metastasis. Methodology: miR expression levels of paired normal and malignant pancreatic tissue samples from ten PDAC patients were analyzed by using their RNA-sequencing data. Then, their cellular and molecular functions as well as the associated molecular signaling pathways with the target genes were identified. The most significant miRs were selected based on their fold changes (FC) and p-value (p<0.05). Data analysis was performed by using SPSS software and specifically paired t-tests between normal and malignant patient tissue samples. Moreover, expression levels of the most significantly altered miRs were further analysed by using Panc-1, CAPAN-2, MiaPaca-2 and Panc10.05 PDAC cell lines. Results: 31 upregulated and 13 downregulated miRs were reported, approximately 3000 target genes were detected to be modulated by abnormally expressed miRs, while the bioinformatic analysis disseminated that the dysregulated miRNAs were correlated to numerous signaling pathways such as EGF-Jak-STAT, KRAS/NRAS and PI3K. The PDAC cell line-based analysis confirmed the aberrant miR expression. Conclusions: Taking the data together, we suggest that specific miR signature profiles could prove useful for PDAC in order to determine patient diagnosis and prognosis. miRs modulate expression of other miRs and/or genes, which are interrelated with metastasis in human neoplasms. In addition, both form mutual feedback circuits, thereby increasing the connectivity and complexity of the regulatory network. Targeting this network will facilitate not only the development and advancement of miR-based clinical applications, but also will illuminate the gap between genotypic and phenotypic features of PDAC. Conclusively, the findings of this research could be the cornerstone of a pioneer precision medicine era of research.

Article numbere19
JournalPancreatology
Journal citation20 (8)
ISSN1424-3903
Year2020
PublisherElsevier
Digital Object Identifier (DOI)https://doi.org/10.1016/j.pan.2020.10.015
Web address (URL)http://dx.doi.org/10.1016/j.pan.2020.10.015
Publication dates
PublishedDec 2020

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Viral Rebound and Emergence of Drug Resistance in the Absence of Viral Load Testing: A Randomized Comparison between Zidovudine-Lamivudine plus Nevirapine and Zidovudine-Lamivudine plus Abacavir
Ndembi, N., Goodall, R.L., Dunn, D.T., McCormick, A.L., Burke, A., Lyagoba, F., Munderi, P., Katundu, P., Kityo, C., Robertson, V., Yirrell, D.L., Walker, A.S., Gibb, D.M., Gilks, C.F., Kaleebu, P. and Pillay, D. 2010. Viral Rebound and Emergence of Drug Resistance in the Absence of Viral Load Testing: A Randomized Comparison between Zidovudine-Lamivudine plus Nevirapine and Zidovudine-Lamivudine plus Abacavir. The Journal of Infectious Diseases. 201 (1), pp. 106-113. https://doi.org/10.1086/648590

Secreted Frizzled-related protein-1 is a negative regulator of androgen receptor activity in prostate cancer
Kawano, Y., Diez, S., Uysal-Onganer, P., Darrington, R.S., Waxman, J. and Kypta, R.M. 2009. Secreted Frizzled-related protein-1 is a negative regulator of androgen receptor activity in prostate cancer. British Journal of Cancer. 100, pp. 1165-1174. https://doi.org/10.1038/sj.bjc.6604976

Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity
Ding, Y., Brackenbury, W.J., Uysal Onganer, P., Montano, X., Porter, L.M., Bates, L.F. and Djamgoz, M.B.A. 2008. Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity. Journal of Cellular Physiology. 215 (1), pp. 77-81. https://doi.org/10.1002/jcp.21289

Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate
McCormick, A.L., Brown, R.H., Cudkowicz, M.E., Al-Chalabi, A. and Garson, J.A. 2008. Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate. Neurology. 70 (4), pp. 278-283. https://doi.org/10.1212/01.wnl.0000297552.13219.b4

The expression and functional characterization of sigma (sigma) 1 receptors in breast cancer cell lines
Aydar, E., Uysal Onganer, P., Perrett, R., Djamgoz, M.B.A. and Palmer, C.P. 2006. The expression and functional characterization of sigma (sigma) 1 receptors in breast cancer cell lines. Cancer Letters. 242 (2), pp. 245-257. https://doi.org/10.1016/j.canlet.2005.11.011

An acetylcholinesterase-derived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line
Uysal Onganer, P., Djamgoz, M.B.A., Whyte, K. and Greenfield, S.A. 2006. An acetylcholinesterase-derived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line. Biochimica et Biophysica Acta: general subjects. 1760 (3), pp. 415-420. https://doi.org/10.1016/j.bbagen.2005.12.016

Small-cell lung cancer (human): potentiation of endocytic membrane activity by voltage-gated Na(+) channel expression in vitro
Uysal Onganer, P. and Djamgoz, M.B.A. 2005. Small-cell lung cancer (human): potentiation of endocytic membrane activity by voltage-gated Na(+) channel expression in vitro. Journal of Membrane Biology. 204, pp. 67-75. https://doi.org/10.1007/s00232-005-0747-6

Neuronal characteristics of small-cell lung cancer
Uysal Onganer, P., Seckl, M.J. and Djamgoz, M.B.A. 2005. Neuronal characteristics of small-cell lung cancer. British Journal of Cancer. 93, pp. 1197-1201. https://doi.org/10.1038/sj.bjc.6602857

An interferon gamma-gp120 fusion delivered as a DNA vaccine induces enhanced priming
Nimal, S., McCormick, A.L., Thomas, M.S. and Heath, A.W. 2005. An interferon gamma-gp120 fusion delivered as a DNA vaccine induces enhanced priming. Vaccine. 23 (10), pp. 3984-3990. https://doi.org/10.1016/j.vaccine.2005.01.160

CD40 antibody as an adjuvant induces enhanced T cell responses
Carlring, J., Barr, T.A., McCormick, A.L. and Heath, A.W. 2004. CD40 antibody as an adjuvant induces enhanced T cell responses. Vaccine. 22 (25-26), p. 3323–3328. https://doi.org/10.1016/j.vaccine.2004.02.043

A potent adjuvant effect of CD40 antibody attached to antigen
Barr, T.A., McCormick, A.L., Carlring, J. and Heath, A.W. 2003. A potent adjuvant effect of CD40 antibody attached to antigen. Immunology. 109 (1), pp. 87-92. https://doi.org/10.1046/j.1365-2567.2003.01634.x

Immunization with an Interferon-g–gp120 Fusion Protein Induces Enhanced Immune Responses to Human Immunodeficiency Virus gp120
McCormick, A.L., Thomas, M.S. and Heath, A.W. 2001. Immunization with an Interferon-g–gp120 Fusion Protein Induces Enhanced Immune Responses to Human Immunodeficiency Virus gp120. The Journal of Infectious Diseases. 184 (11), pp. 1423-1430. https://doi.org/10.1086/324371

Gag Determinants of Fitness and Drug Susceptibility in Protease Inhibitor-Resistant Human Immunodeficiency Virus Type 1
Parry, C.M., Kohli, A., Boinett, C.J., Towers, G.J., McCormick, A.L. and Pillay, D. 1999. Gag Determinants of Fitness and Drug Susceptibility in Protease Inhibitor-Resistant Human Immunodeficiency Virus Type 1. Journal of Virology. 83 (18), pp. 9094-9101. https://doi.org/10.1128/JVI.02356-08

Cell Surface Expression of CD154 Inhibits Alloantibody Responses: A Mechanism for the Prevention of Autoimmune Responses against Activated T Cells?
McCormick, A.L., Santos-Argumedo, L., Thomas, M.S. and Heath, A.W. 1999. Cell Surface Expression of CD154 Inhibits Alloantibody Responses: A Mechanism for the Prevention of Autoimmune Responses against Activated T Cells? Cellular Immunology. 195 (2), pp. 157-161. https://doi.org/10.1006/cimm.1999.1528

Enhancement of immunogenicity of recombinant antigens by production of a cytokine-antigen fusion protein for vaccination
McCormick, A.L., Thomas, M.S. and Heath, A.W. 1997. Enhancement of immunogenicity of recombinant antigens by production of a cytokine-antigen fusion protein for vaccination. Biochemical Society Transactions. 25, p. 297S. https://doi.org/10.1042/bst025297s

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