Abstract
BackgroundCircular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs formed by a covalently closed loop, and increasing evidence has revealed that circRNAs play crucial functions in regulating gene expression. CircSLC8A1 is a circRNA generated from the SLC8A1 gene. Currently, the role and underlying molecular mechanisms of circSLC8A1 in bladder cancer remain unknown.MethodsThe differentially expressed circRNAs were identified from RNA-sequencing data, and circSLC8A1 was determined as a new candidate circRNA. qRT-PCR was used to detect the expression of circRNAs, miRNAs and mRNAs in human tissues and cells. RNA pull-down assay and luciferase reporter assay were used to investigate the interactions between the specific circRNA, miRNA and mRNA. The effects of circSLC8A1 on bladder cancer cells were explored by transfecting with plasmids in vitro and in vivo. The expression of PTEN was detected by Western blot. The biological roles were measured by wound healing assay, transwell assay, and CCK-8 assay.ResultsIn the present study, we found that circSLC8A1 was down-regulated in bladder cancer tissues and cell lines, and circSLC8A1 expression was associated with the pathological stage and histological grade of bladder cancer. Over-expression of circSLC8A1 inhibited cell migration, invasion and proliferation both in vitro and in vivo. Mechanistically, circSLC8A1 could directly interact with miR-130b/miR-494, and subsequently act as a miRNA sponge to regulate the expression of the miR-130b/miR-494 target gene PTEN and downstream signaling pathway, which suppressed the progression of bladder cancer.ConclusionsCircSLC8A1 acts as a tumor suppressor by a novel circSLC8A1/miR-130b, miR-494/PTEN axis, which may provide a potential biomarker and therapeutic target for the management of bladder cancer.
Highlights
Circular RNAs are a novel class of endogenous noncoding RNAs formed by a covalently closed loop, and increasing evidence has revealed that circular RNA (circRNA) play crucial functions in regulating gene expression
The results showed that two of the five circRNAs were significantly down-regulated in bladder cancer tissues, and circSLC8A1 was the most down-regulated circRNA according to the quantitative RT-PCR (qRT-PCR) results (Additional file 1: Figure S1). circSLC8A1 arose from the SLC8A1 gene and consisted of the head-totail splicing of exon 1 (1832 bp) (Fig. 1a)
We found that circSLC8A1 was down-regulated in bladder cancer from another RNA-sequencing data set (Log2FC = 3.31) [22], and circSLC8A1 is abundant in early-stage bladder cancer tissues [23]
Summary
Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs formed by a covalently closed loop, and increasing evidence has revealed that circRNAs play crucial functions in regulating gene expression. The role and underlying molecular mechanisms of circSLC8A1 in bladder cancer remain unknown. In China, the mortality and morbidity of bladder cancer ranked first among all the tumors of urinary system [2]. Circular RNA (circRNA) is a novel class of endogenous noncoding RNA molecules generally characterized. Salient features of circRNAs include significant stability, high abundance, evolutionary conservation, and tissue-specific expression [9, 10]. Genome-wide analyses of RNA sequencing data have identified large amounts of circRNAs and proven that they are endogenous, abundant and conserved in mammalian cells, suggesting specific roles of circRNAs in cellular physiology [6, 9]. Many circRNAs have been demonstrated to have critical roles in the carcinogenesis and development of cancers [13, 14]
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