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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
MicroRNA-223-3p inhibits human bladder cancer cell migration and invasion
Ju Guo1, Runfu Cao1, Xingwei Yu1
1Institute of Urology, First Affiliated Hospital of Nanchang University, Nanchang, China.
Abstract:
The regulation of initiation and progression during carcinogenesis of bladder carcinoma is not completely elucidated. Dysregulation of microRNAs has been detected to play critical roles in the development of various cancers, including bladder carcinoma, whereas the involvement of miR-223-3p in the tumorigenesis of bladder carcinoma has not been studied. Here, we show that significantly higher levels of nuclear receptor coactivator 1 and significantly lower levels of miR-223-3p were detected in bladder carcinoma tissue, compared to the adjacent non-tumor tissue. In addition, the levels of nuclear receptor coactivator 1 and miR-223-3p were inversely correlated. Moreover, low miR-223-3p levels in bladder carcinoma specimens were associated with poor prognosis. In vitro, depletion of miR-223-3p increased bladder carcinoma cell invasion, which was abolished by overexpression of nuclear receptor coactivator 1. Bioinformatics studies demonstrate that miR-223-3p may bind to the 3'-UTR of nuclear receptor coactivator 1 messenger RNA to inhibit its protein translation in bladder carcinoma cells. Together, our study highlights miR-223-3p as a previously unrecognized microRNA that inhibits bladder carcinoma invasiveness via nuclear receptor coactivator 1, and this finding may be important for developing innovative therapeutic targets in treating bladder carcinoma.
Insights
MicroRNA-223-3p (miR-223-3p) acts as a tumor suppressor in bladder carcinoma. Lower miR-223-3p levels correlate with increased cancer cell invasion and poor prognosis, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Carcinogenesis of bladder carcinoma involves complex regulatory pathways.
- MicroRNA dysregulation is implicated in various cancers, but miR-223-3p's role in bladder cancer is unstudied.
- Nuclear receptor coactivator 1 (NCOA1) levels are altered in bladder carcinoma.
Purpose of the Study:
- To investigate the role of miR-223-3p in bladder carcinoma tumorigenesis.
- To explore the relationship between miR-223-3p and NCOA1 in bladder cancer.
- To determine the prognostic significance of miR-223-3p in bladder carcinoma patients.
Main Methods:
- Quantitative analysis of miR-223-3p and NCOA1 expression in tumor and adjacent non-tumor tissues.
- In vitro cell invasion assays with miR-223-3p depletion and NCOA1 overexpression.
- Bioinformatics analysis to predict miR-223-3p binding sites on NCOA1 mRNA.
Main Results:
- Bladder carcinoma tissues exhibit significantly higher NCOA1 and lower miR-223-3p levels compared to non-tumor tissues.
- NCOA1 and miR-223-3p levels are inversely correlated.
- Low miR-223-3p expression is associated with poor prognosis and increased cancer cell invasion.
- miR-223-3p inhibits bladder carcinoma cell invasion by suppressing NCOA1 translation.
Conclusions:
- miR-223-3p is a novel tumor suppressor microRNA in bladder carcinoma.
- miR-223-3p inhibits bladder cancer cell invasiveness by targeting NCOA1.
- This finding offers potential for developing new therapeutic strategies for bladder carcinoma.
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