Novel microRNAs modulating ecto-5′-nucleotidase expression

• Verfasst von: Kordaß, Theresa [VerfasserIn]
• Verfasst von: Chao, Tsu-Yang [VerfasserIn]
• Verfasst von: Osen, Wolfram [VerfasserIn]
• Verfasst von: Eichmüller, Stefan B. [VerfasserIn]
• Titel: Novel microRNAs modulating ecto-5′-nucleotidase expression
• Verf.angabe: Theresa Kordaß, Tsu-Yang Chao, Wolfram Osen and Stefan B. Eichmüller
• E-Jahr: 2023
• Jahr: 20 June 2023
• Umfang: 20 S.
• Fussnoten: Gesehen am 15.08.2023
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2023
• Band/Heft Quelle: 14(2023), Artikel-ID 1199374, Seite 1-20
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2023.1199374
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1856241521

Abstract

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.