Bogusławska Joanna, Rakhmetullina Aizhan, Grzanka Małgorzata, Białas Alex, Rybicka Beata, Życka-Krzesińska Joanna, Molcan Tomasz, Zielenkiewicz Piotr, Pączek Leszek, Piekiełko-Witkowska Agnieszka
Department of Biochemistry and Molecular Biology, Centre of Translational Research, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland.
Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawińskiego 5a, 02-106 Warsaw, Poland.
Genes (Basel). 2025 Feb 27;16(3):293. doi: 10.3390/genes16030293.
: microRNAs are small non-coding RNAs that regulate gene expression by inducing mRNA degradation or inhibiting translation. A growing body of evidence suggests that miRNAs may be utilized as anti-cancer therapeutics by targeting expression of key genes involved in cancerous transformation and progression. Renal cell cancer (RCC) is the most common kidney malignancy. The most efficient RCC treatments involve blockers of immune checkpoints, including antibodies targeting PD-L1 (Programmed Death Ligand 1). Interestingly, recent studies revealed the cross-kingdom horizontal transfer of plant miRNAs into mammalian cells, contributing to the modulation of gene expression by food ingestion. Here, we hypothesized that PD-L1 expression may be modulated by miRNAs originating from edible plants. : To verify this hypothesis, we performed bioinformatic analysis to identify mes-miR395e from (cassava) as a promising candidate miRNA that could target PD-L1. To verify PD-L1 regulation mediated by the predicted plant miRNA, synthetic mes-miR395 mimics were transfected into cell lines derived from RCC tumors, followed by evaluation of PD-L1 expression using qPCR and Western blot. : Transfection of mes-miR395e mimics into RCC-derived cell lines confirmed that this miRNA decreases expression of PD-L1 in RCC cells at both mRNA and protein levels. : This preliminary study shows the promise of plant miRNA as potential adjuvants supporting RCC treatment.
微小RNA是一类小的非编码RNA,通过诱导mRNA降解或抑制翻译来调节基因表达。越来越多的证据表明,微小RNA可通过靶向参与癌变和进展的关键基因的表达,用作抗癌治疗药物。肾细胞癌(RCC)是最常见的肾脏恶性肿瘤。最有效的肾细胞癌治疗方法包括免疫检查点阻滞剂,包括靶向程序性死亡配体1(PD-L1)的抗体。有趣的是,最近的研究揭示了植物微小RNA向哺乳动物细胞的跨界水平转移,通过食物摄入影响基因表达的调控。在此,我们假设PD-L1的表达可能受到来自可食用植物的微小RNA的调控。为了验证这一假设,我们进行了生物信息学分析,从木薯中鉴定出mes-miR395e作为一个有潜力的候选微小RNA,它可能靶向PD-L1。为了验证预测的植物微小RNA介导的PD-L1调控,将合成的mes-miR395模拟物转染到源自肾细胞癌肿瘤的细胞系中,随后使用qPCR和蛋白质免疫印迹法评估PD-L1的表达。将mes-miR395e模拟物转染到源自肾细胞癌的细胞系中证实,这种微小RNA在mRNA和蛋白质水平上均降低了肾细胞癌中PD-L1的表达。这项初步研究表明,植物微小RNA有望作为支持肾细胞癌治疗的潜在佐剂。