Project description: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.

| S-EPMC10318900 | biostudies-literature

Novel microRNAs modulating ecto-5′-nucleotidase expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-31 | GSE228642 | GEO

Novel microRNAs modulating ecto-5′-nucleotidase expression [MaMel]

Project description:the effect of NT5E enhancing miRNAs was studied by gene expression profiling to unterstand mechanism of observed NT5E upregulation.

2023-05-31 | GSE228640 | GEO

Novel microRNAs modulating ecto-5′-nucleotidase expression [MDA-MB-231]

Project description:the effect of NT5E enhancing miRNAs was studied by gene expression profiling to unterstand mechanism of observed NT5E upregulation.

2023-05-31 | GSE228639 | GEO

Novel microRNAs modulating ecto-5′-nucleotidase expression [SK-Mel-28]

Project description:the effect of NT5E enhancing miRNAs was studied by gene expression profiling to unterstand mechanism of observed NT5E upregulation.

2023-05-31 | GSE228641 | GEO

Ecto-5’-Nucleotidase (Nt5e/CD73)-Mediated Adenosine Signaling Attenuates TGFβ-2 Induced Elastin and Cellular Contraction

Project description:Ecto-5’-Nucleotidase (Nt5e/CD73)-Mediated Adenosine Signaling Attenuates TGFβ-2 Induced Elastin and Cellular Contraction

| PRJNA895057 | ENA

Cerebrospinal fluid ecto-GPR37 in Parkinson’s disease

Project description:Improved diagnostic and prognostic biomarkers which reflect pathological progression would benefit the management of Parkinson’s disease. GPR37, also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein-coupled receptor, which has a defective parkin-mediated ubiquitination in autosomal recessive Parkinson’s disease. By means of immunoblot and mRNA determinations we detected increased GPR37 levels in postmortem substantia nigra from Parkinson’s disease subjects. We revealed the presence of the N-terminal domain of GPR37 (ecto-GPR37) in human and mouse cerebrospinal fluid (CSF). We engineered a Nanoluciferase-based ELISA to evaluate ecto-GPR37 in CSF and demonstrated the presence of ecto-GPR37 in CSF from wild-type, but not from GPR37-/-, mice. Subsequently, the relative abundance of ecto-GPR37 in CSF in healthy controls (n=48) and Parkinson’s disease (n=45) patients was assessed. Interestingly, we found that ecto-GPR37 was significantly increased (P = 0.0002) in the CSF from Parkinson’s disease patients. Importantly, mass spectrometric analysis of immunoprecipitation of GPR37 in CSF supported the analytical validity of our ELISA to measure ecto-GPR37 in human CSF. Overall, these results open exciting perspectives and encourage further systemically studies to confirm the clinical validity and utility of ecto-GPR37 as a potential Parkinson’s disease diagnostic/prognostic biomarker

2021-05-13 | PXD015619 | Pride

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