miR-224-5p Contained in Urinary Extracellular Vesicles Regulates PD-L1 Expression by Inhibiting Cyclin D1 in Renal Cell Carcinoma Cells.
miR-224-5p Contained in Urinary Extracellular Vesicles Regulates PD-L1 Expression by Inhibiting Cyclin D1 in Renal Cell Carcinoma Cells.
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尿胞外小泡中的MIR-224-5P通过抑制细胞周期蛋白D1调节肾癌细胞PD-L1的表达。
DOI：
10.3390/cancers13040618
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发表时间：
2021-02-04
期刊：
影响因子：
5.2
通讯作者：
Zeng S
中科院分区：
文献类型：
--
作者：
Qin Z;Hu H;Sun W;Chen L;Jin S;Xu Q;Liu Y;Yu L;Zeng S
细胞外囊泡（EV）中含有丰富的microRNA对肾细胞癌（RCC）进展的详细影响尚不清楚。本研究鉴定了RCC患者尿EV中miR-224- 5 p的过表达。miR-224- 5 p通过抑制cyclin D1的表达，抑制肾癌细胞增殖，并诱导细胞周期阻滞。miR-224- 5 p增加PD-L1蛋白丰度，并且这种调节可以通过EV细胞间传递。这些发现可能有助于发现RCC免疫治疗的生物标志物。尿细胞外囊泡（EV）中丰富的miRNA是发现生物标志物的理想储存库，特别是在肾细胞癌（RCC）中。然而，肾细胞癌中尿EV中所含microRNA的含量和生物学功能仍不明确。在这项研究中，从RCC患者和健康志愿者中分离并表征了尿液EV。通过小RNA测序筛选尿EV中差异表达的microRNA。通过多方面的方法对所选microRNA的靶基因和生物学功能进行了研究。结果表明，与健康志愿者相比，RCC患者的尿EV中miR-224- 5 p显著上调。miR-224- 5 p过表达可抑制肾癌细胞增殖并诱导细胞周期阻滞。通过预测和验证，发现编码cyclin D1的基因CCND 1是miR-224- 5 p的直接靶基因。此外，miR-224- 5 p可增强肾癌细胞的侵袭和转移能力。有趣的是，miR-224- 5 p还通过抑制CCND 1增加了PD-L1蛋白的稳定性。这种作用可以通过EV传递，并进一步促进RCC细胞对T细胞依赖性毒性的抵抗。总之，含有miR-224- 5 p的尿EV被鉴定为RCC中的潜在生物标志物。miR-224- 5 p通过抑制CCND 1调节PD-L1蛋白表达阐明了miR-224 - 5 p在RCC进展中的新作用。
The detailed effects of abundant microRNAs contained in extracellular vesicles (EVs) on renal cell carcinoma (RCC) progression are still unclear. This study identified the overexpression of miR-224-5p in urinary EVs of RCC patients. miR-224-5p suppressed RCC cell proliferation and induced cell cycle arrest through inhibiting cyclin D1 expression. PD-L1 protein abundance was increased by miR-224-5p, and this regulation could be transmitted via EVs intercellularly. These findings may shed light on biomarker discovery for RCC immunotherapy. 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 CCND1 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 CCND1. 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 CCND1 elucidates new roles of miR-224-5p in RCC progression.
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影响因子：
--
作者：
Fujii N;Hirata H;Ueno K;Mori J;Oka S;Shimizu K;Kawai Y;Inoue R;Yamamoto Y;Matsumoto H;Shimabukuro T;Udoh K;Hoshii Y;Dahiya R;Matsuyama H
通讯作者：
Matsuyama H
影响因子：
6
作者：
Lichner, Zsuzsanna;Mejia-Guerrero, Salvador;Yousef, George M.
通讯作者：
Yousef, George M.
miR-489-3p 和 miR-630 的上调通过靶向 OCT2 抑制肾细胞癌中奥沙利铂的摄取
影响因子：
14.5
作者：
Chen, Lu;Chen, Le;Yu, Lushan
通讯作者：
Yu, Lushan
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators
影响因子：
4
作者：
Li, Jianchang;Liu, Xiuming;Wang, Wenqi
通讯作者：
Wang, Wenqi