Dataset Information

CiRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653.

ABSTRACT: 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.

SUBMITTER: Su Y

PROVIDER: S-EPMC6932879 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653.

Su Yinjie Y Feng Weilian W Zhong Guanglei G Ya Yiyao Y Du Zehu Z Shi Juanyi J Chen Luping L Dong Wen W Lin Tianxin T

Aging 20191210 23

<h4>Background</h4>Circular RNAs have been widely explored as potential biomarkers and therapeutic targets in bladder cancer; however, few have been functionally characterized.<h4>Results</h4>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 ubi ...[more]

PMID: 31819015

Similar Datasets

Project description:Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR]?=?2.75, 95% confidence interval [CI] 1.74-6.51, p?=?0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR-7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.

Dataset Information

CiRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653.

Publications

ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure