ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653
Yinjie Su1, Weilian Feng2, Guanglei Zhong3
1The Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Background:
Circular RNAs have been widely explored as potential biomarkers and therapeutic targets in bladder cancer; however, few have been functionally characterized.
Results:
ciRs-6 is expressed at low levels in cancer tissues and advanced tumor grades and stages, and its expression correlates with better outcomes for bladder cancer patients. In vitro and in vivo, ciRs-6 was shown to suppress bladder cancer growth by sponging miR-653 to elevate March1 levels. March1 is an E3 ubiquitin ligase that has been proven to suppress bladder cancer growth; knocking down March1 in ciRs-6 overexpressed bladder cancer cells reversed the tumor suppressive effect of ciRs-6.
Conclusions:
Our study identifies an oncogenic role of ciRs-6 and suggests its usefulness as a novel biomarker for bladder cancer diagnosis and prognosis and as a therapeutic target for bladder cancer.
Methods:
ciRs-6 was identified by RNA-seq and qPCR; CCK8 assays, clone forming assays and cell cycle analyses were performed to evaluate the in vitro effect of ciRs-6 in bladder cancer; further, a mouse subcutaneous tumor model was designed for in vivo analysis. RNA pulldown assays, miRNA capture experiments and dual luciferase assessments were applied for mechanistic studies.
Insights
Circular RNAs (ciRs-6) show a tumor-suppressive role in bladder cancer, inhibiting growth by regulating miR-653 and March1. This suggests ciRs-6 as a potential biomarker and therapeutic target for bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers.
- Few circRNAs have been functionally characterized in the context of bladder cancer.
- Understanding circRNA function is crucial for developing novel diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the functional role of ciRs-6 in bladder cancer.
- To explore the potential of ciRs-6 as a biomarker for bladder cancer diagnosis and prognosis.
- To identify ciRs-6 as a therapeutic target for bladder cancer treatment.
Main Methods:
- RNA sequencing (RNA-seq) and quantitative polymerase chain reaction (qPCR) for ciRs-6 identification.
- In vitro assays (CCK8, colony formation, cell cycle analysis) to assess ciRs-6's effect on bladder cancer cells.
- In vivo mouse subcutaneous tumor models to evaluate tumor growth.
- Molecular mechanism studies including RNA pulldown, miRNA capture, and dual luciferase assays.
Main Results:
- ciRs-6 expression is downregulated in bladder cancer tissues and correlates with advanced tumor stages.
- Low ciRs-6 expression is associated with better patient outcomes.
- ciRs-6 suppresses bladder cancer growth in vitro and in vivo by sponging miR-653, leading to increased March1 levels.
- March1, an E3 ubiquitin ligase, was confirmed to suppress bladder cancer growth, and its knockdown reversed ciRs-6's tumor-suppressive effect.
Conclusions:
- ciRs-6 exhibits an oncogenic role in bladder cancer.
- ciRs-6 serves as a potential novel biomarker for bladder cancer diagnosis and prognosis.
- ciRs-6 represents a promising therapeutic target for bladder cancer.
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