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Expression profiles of Natural Killer Group 2D Ligands (NGK2DLs) in colorectal carcinoma and changes in response to chemotherapeutic agents

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Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Natural Killer Group 2D Receptor (NKG2D) and their ligands (NKG2DLs) play crucial roles in natural killer (NK) cell-mediated cytotoxicity. Tumorigeneses cause increased NKG2DLs expression on tumor cell surfaces, thereby these cells individually eliminated by NK cells. However, CRC cells can reduce their NKG2DL expression to escape from NK-mediated immune surveillance which is associated with poor prognosis. Therefore, previous studies suggest that up-regulation of NKG2DLs can contribute to promising NK cell-mediated immunotherapy strategies. We aimed to analyze NKG2DLs expression profiles in response to chemotherapeutic drugs and increased MHC class I polypeptide-related sequence A (MICA) expression, which is related to favorable prognosis in CRC, using low doses of bortezomib and epirubicin combination without causing direct cytotoxicity. Results showed that MICA expression  sligthly increased following drug treatment in the CRC cells but not for the normal cells. Also, we enriched our study with Gene Expression Omnibus (GEO) datasets including expression profiles of various NKG2DLs using in silico analyses. Accordingly, NKG2DL expression in CRC was screened in proportion to other cancers, histologic subtypes, TNM stages and metastatic samples to compare with our data. Overall, the analyzed data showed that NKG2DLs demonstrate different expression profiles in response to chemotherapeutic agents and a combination of low-dose bortezomib and epirubicin slightly increased MICA mRNA expression in CRC cell lines. However, performing further analysis of the combination therapy for MICA protein expression and studying its interaction with NK cells will make the results more meaningful.

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Data availability

All the microarray data and probe ids can be found in the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/).

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Acknowledgements

The authors feel thankful to Caglar Berkel for his contributions and Tokat Gaziosmanpasa University Scientific Research Projects Office (BAP) for funding.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research was supported by Tokat Gaziosmanpasa University, Scientific Research Projects, No: 2019/15.

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  1. Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, 60250, Tokat, Turkey

    Burak Kucuk, Esra Yilmaz & Ercan Cacan

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EC: Supervising, planning methodology and constructing hypothesis for research and manuscript. BK, EY and EC: Execution of the experiments, data management, analysis and constructing of the body of the manuscript.

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Correspondence to Ercan Cacan.

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Kucuk, B., Yilmaz, E. & Cacan, E. Expression profiles of Natural Killer Group 2D Ligands (NGK2DLs) in colorectal carcinoma and changes in response to chemotherapeutic agents. Mol Biol Rep 48, 3999–4008 (2021). https://doi.org/10.1007/s11033-021-06404-y

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