ArticleClinical and translational medicine2022
Identification and characterization of novel CD274 (PD-L1) regulating microRNAs and their functional relevance in melanoma.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- miR-155-5p drives coordinated tumor and macrophage reprogramming across multiple cancer entities.BMC medicine · 2026Article
- Integrative transcriptomic and structural modeling reveal CASP1, TLR3, PYCARD, and CD274 as immune-modulatory drivers in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Role of tumor‑infiltrating lymphocytes and miR‑155 in breast cancer: Insights into carcinogenesis and their potential as prognostic biomarkers (Review).Oncology reports · 2026Review
- Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy.Journal for immunotherapy of cancer · 2024Review
- Transcriptomics analysis reveals potential mechanisms underlying mitochondrial dysfunction and T cell exhaustion in astronauts' blood cells in space.Frontiers in immunology · 2024Article
- Identification and characterization of novel CD274 (PD-L1) regulating microRNAs and their functional relevance in melanoma.Clinical and translational medicine · 2022Article
- Identification and validation of a TTN-associated immune prognostic model for skin cutaneous melanoma.Frontiers in genetics · 2022Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors directed against programmed cell death 1 (PDCD1/PD1) receptor and programmed cell death-ligand 1 (CD274/PD-L1) have been recently successfully implemented for the treatment of many cancers, but the response rate of tumour patients is still limited due to intrinsic and acquired resistances. However, the underlying molecular mechanisms of this limited response have still to be defined in detail. The aim of this study is to uncover processes inhibiting PDCD1/CD274 expression thereby enhancing anti-tumour immune responses. The identification and characterization of microRNAs (miRNAs) targeting the 3'-untranslated region (3'-UTR) as well as the coding sequence (CDS) of CD274 will provide the basis for a new drug development.
methodsHuman melanoma cell lines and tissue samples were subjected to mRNA and/or protein expression analysis using qPCR, Western blot, flow cytometry, and/or immunohistochemistry. The data were correlated to clinical parameters. MiRNA trapping by RNA in vitro affinity purification (miTRAP) technology in combination with small RNA sequencing and different bioinformatics tools were employed to identify CD274-regulating miRNAs.
resultsScreening based on miTRAP in combination with RNAseq identified a large number of novel CD274-regulating candidate miRNAs, from which eight selected miRNAs were functionally validated. Five out of eight miRNAs were able to significantly reduce CD274 surface expression indicating that these miRNAs directly bind to the 3'-UTR or CDS of the CD274 gene. The miRNA-mediated inhibition of CD274 expression was accompanied by an increased T cell recognition. Furthermore, an inverse expression of three CD274-regulating miRNAs and CD274 was demonstrated in melanoma lesions. A CD274 miRNA score was generated, which was associated with disease progression and reduced survival of melanoma patients.
conclusionsThese data revealed a novel mechanism that miRNAs targeting the CDS of immune checkpoint genes are functional, have prognostic relevance, and also the potential for the development of novel miRNA-based therapies.
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