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长链非编码 RNA BCYRN1 作为膀胱癌血清外泌体中潜在的治疗靶点和诊断标志物。

LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer.

机构信息

Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.

出版信息

Int J Mol Sci. 2024 May 29;25(11):5955. doi: 10.3390/ijms25115955.

Abstract

Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 () in BC. We performed loss-of-function assays to examine the effects of downregulation in T24 and BOY BC cells. We found that downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal as a biomarker. Clinically, expression in serum exosomes from patients with BC ( = 31) was significantly higher than that in healthy donors ( = 19; mean difference: 4.1-fold higher, < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal levels were significantly decreased ( = 8). Thus, serum exosomal may be a promising diagnostic marker and therapeutic target in patients with BC.

摘要

膀胱癌(BC)是一种常见的泌尿生殖系统恶性肿瘤,由于缺乏诊断标志物和有限的有效治疗方法,其发病率和死亡率都很高。在这里,我们评估了长链非编码 RNA 脑细胞质 RNA 1()在 BC 中的作用。我们进行了功能丧失实验,以研究下调 T24 和 BOY BC 细胞中的作用。我们发现下调显著抑制了 BC 细胞的增殖、迁移、侵袭和三维球体形成能力,并诱导了细胞凋亡。此外,使用肿瘤部分的 RNA 序列进行基因集富集分析(GSEA)表明下调降低了与细胞周期相关的 mRNA 的表达。这些发现得到了流式细胞术检测到 G/M 期阻滞的观察结果的支持。最后,我们检查了血清外泌体作为生物标志物的表达。临床方面,BC 患者(=31)血清外泌体中的表达明显高于健康供体(=19;平均差异:高 4.1 倍,<0.01)。此外,在接受 BC 完全切除的患者中,血清外泌体水平显著降低(=8)。因此,血清外泌体可能是 BC 患者有前途的诊断标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8f8/11172611/b04fd8b814f4/ijms-25-05955-g001.jpg

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