miR-224-5p Contained in Urinary Extracellular Vesicles Regulates PD-L1 Expression by Inhibiting Cyclin D1 in Renal Cell Carcinoma Cells

The abundant miRNAs in urinary extracellular vesicles (EVs) represent ideal reservoirs for biomarker discovery, especially in renal cell carcinoma (RCC). However, the content and biological functions of microRNAs contained in urinary EVs in RCC remain ambiguous. In this study, urinary EVs were isola...

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Bibliographic Details
Published in:Cancers 2021-02, Vol.13 (4), p.618
Main Authors: Qin, Zhiyuan, Hu, Haihong, Sun, Wen, Chen, Lu, Jin, Shengnan, Xu, Qingwen, Liu, Yuxi, Yu, Lushan, Zeng, Su
Format: Article
Language:English
Subjects:
Binding sites
Bioinformatics
Biomarkers
Cell cycle
Cell growth
Cell proliferation
Cyclin D1
Cyclin-dependent kinases
Extracellular vesicles
Immunotherapy
Invasiveness
Kidney cancer
Kinases
L1 protein
Ligands
Lymphocytes T
Metastases
MicroRNAs
miRNA
PD-L1 protein
Proteins
Renal cell carcinoma
Toxicity
Urine
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Summary:The abundant miRNAs in urinary extracellular vesicles (EVs) represent ideal reservoirs for biomarker discovery, especially in renal cell carcinoma (RCC). However, the content and biological functions of microRNAs contained in urinary EVs in RCC remain ambiguous. In this study, urinary EVs were isolated and characterized from RCC patients and healthy volunteers. Differentially expressed microRNAs in urinary EVs were screened by small RNA sequencing. The target gene and biological functions of selected microRNAs were investigated through multifaceted methods. Results indicated that miR-224-5p was significantly upregulated in urinary EVs of RCC patients compared to healthy volunteers. The overexpression of miR-224-5p inhibited RCC cell proliferation and induced cell cycle arrest. The gene encoding cyclin D1 was identified as a direct target of miR-224-5p via prediction and validation. Moreover, the invasive and metastatic abilities of RCC cells were enhanced by miR-224-5p. Interestingly, miR-224-5p also increased the stability of PD-L1 protein by inhibiting . This effect could be transmitted via EVs and further promoted the resistance of RCC cells to T cell-dependent toxicity. In summary, urinary EVs containing miR-224-5p were identified as a potential biomarker in RCC. Regulation of PD-L1 protein expression by miR-224-5p through suppressing elucidates new roles of miR-224-5p in RCC progression.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13040618