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

Author:

Arima Junya1ORCID,Yoshino Hirofumi1ORCID,Fukumoto Wataru1,Kawahara Ichiro1,Saito Saeki1,Li Gang1,Fukuda Ikumi1,Iizasa Sayaka1,Mitsuke Akihiko1,Sakaguchi Takashi1,Inoguchi Satoru1,Matsushita Ryosuke1,Nakagawa Masayuki1,Tatarano Shuichi1ORCID,Yamada Yasutoshi1,Enokida Hideki1

Affiliation:

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

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 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 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 BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

Funder

Japan Society for the Promotion of Science KAKENHI

Kodama Memorial Fund for Medical Research

Publisher

MDPI AG

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