Novel microRNAs modulating ecto-5′-nucleotidase expression
IntroductionThe expression of immune checkpoint molecules (ICMs) by cancer cells is known to counteract tumor-reactive immune responses, thereby promoting tumor immune escape. For example, upregulated expression of ecto-5′-nucleotidase (NT5E), also designated as CD73, increases extracellular levels...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 June 2023
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| In: |
Frontiers in immunology
Year: 2023, Volume: 14, Pages: 1-20 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2023.1199374 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2023.1199374 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1199374 
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| Author Notes: | Theresa Kordaß, Tsu-Yang Chao, Wolfram Osen and Stefan B. Eichmüller |
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| 520 | |a IntroductionThe expression of immune checkpoint molecules (ICMs) by cancer cells is known to counteract tumor-reactive immune responses, thereby promoting tumor immune escape. For example, upregulated expression of ecto-5′-nucleotidase (NT5E), also designated as CD73, increases extracellular levels of immunosuppressive adenosine, which inhibits tumor attack by activated T cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Thus, the binding of miRNAs to the 3′-untranslated region of target mRNAs either blocks translation or induces degradation of the targeted mRNA. Cancer cells often exhibit aberrant miRNA expression profiles; hence, tumor-derived miRNAs have been used as biomarkers for early tumor detection.MethodsIn this study, we screened a human miRNA library and identified miRNAs affecting the expression of ICMs NT5E, ENTPD1, and CD274 in the human tumor cell lines SK-Mel-28 (melanoma) and MDA-MB-231 (breast cancer). Thereby, a set of potential tumor-suppressor miRNAs that decreased ICM expression in these cell lines was defined. Notably, this study also introduces a group of potential oncogenic miRNAs that cause increased ICM expression and presents the possible underlying mechanisms. The results of high-throughput screening of miRNAs affecting NT5E expression were validated in vitro in 12 cell lines of various tumor entities.ResultsAs result, miR-1285-5p, miR-155-5p, and miR-3134 were found to be the most potent inhibitors of NT5E expression, while miR-134-3p, miR-6859-3p, miR-6514-3p, and miR-224-3p were identified as miRNAs that strongly enhanced NT5E expression levels.DiscussionThe miRNAs identified might have clinical relevance as potential therapeutic agents and biomarkers or therapeutic targets, respectively. | ||
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