Circular RNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating PTEN

Abstract

Background: 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. CircSLC8A1 is a circRNA generated from the SLC8A1 gene. Currently, the role and underlying molecular mechanisms of circSLC8A1 in bladder cancer remain unknown. Methods: The 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. Results: In 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. Conclusions: CircSLC8A1 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. Background Bladder cancer is the most common malignancy of the urinary system and is one of the most prevalent malignancies worldwide [1]. In China, the mortality and morbidity of bladder cancer ranked first among all the tumors of urinary system [2]. Bladder cancer can be classified into two types according to the depth of tumor invasion: non-muscle invasive tumor (70~80%) and muscle-invasive tumor (20~30%) [3].For the patients with muscle-invasive bladder cancer, the occurrence of metastasis is more frequent, and the prognosis is poorer [4]. Even in those muscle-invasive bladder cancer patients who receive optimal treatment with surgery and chemotherapy, the 5-year overall survival rate is only 60% due to distant metastasis [5]. Therefore, it is of great clinical significance to clarify the molecular mechanisms that drive the progression of bladder cancer, which will help to develop more effective anticancer therapies. Circular RNA (circRNA) is a novel class of endogenous noncoding RNA molecules generally characterized

Circular RNA circHIAT1 inhibits proliferation and epithelial‐mesenchymal transition of gastric cancer cell lines through downregulation of miR‐21

“…[ 25 ] For example, circSLC8A1 was proved to be a tumor inhibitor via the circSLC8A1/miR‐130b and miR‐494/PTEN axis in bladder cancer. [ 26 ] Moreover, many circRNAs were reported to be involved in GC development, including promotion and inhibition. Huang et al [ 27 ] found that circRNA hsa_circ_0008035 promoted proliferation and incursion in GC cells.…”

Circular RNA USP1 regulates the permeability of blood‐tumour barrier via miR‐194‐5p/FLI1 axis

“…The interaction between miRNA and circRNA may competitively affect miRNA-mediated regulation of their target genes. [38][39][40] In oral squamous cell carcinoma cells, circ_100290 plays oncogene function by binding with miR-29b. 41 We demonstrated that circ-USP1 may interact with miR-194-5p and function as an endogenous miR-194-5p sponge.…”

Circular RNA circ‑ACACA regulates proliferation, migration and glycolysis in non‑small‑cell lung�carcinoma via miR‑1183 and PI3K/PKB pathway

“…Circular RNAs (circRNAs), a type of single-stranded RNAs which form a covalently closed continuous loop, are produced by backsplicing (4) and they are resistant to exonuclease-mediated degradation (5). Growing evidence has proved that circRNAs are associated with colon cancer (6), gastric cancer (7), bladder cancer (8) and NScLc (9,10). Microarray data showed that hsa_circ_0106705 (circ-ACACA) was upregulated in human lung cancer according to Yang et al (11).…”