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Circular RNA_0000629 Suppresses Bladder Cancer Progression Mediating MicroRNA-1290/CDC73
Jiansong Wang1, Jianjun Luo1, Xuecheng Wu1
1Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, People's Republic of China.
Background:
Recent studies showed circular RNAs (circRNAs) played regulatory roles in bladder cancer (BC). However, the relevance of circ_0000629, a newly identified circRNA, has not been determined yet. We aimed to characterize the function of circ_0000629 in BC and the relevant mechanism.
Methods:
First, we downloaded circRNA-related microarrays GSE147985 and GSE92675 from the GEO database, followed by a validation in our clinically obtained samples. We then overexpressed circ_0000629 in T24 and SW780 cells and evaluated the effects of circ_0000629 on BC cell proliferatory, apoptotic, and metastatic abilities. We further detected the subcellular localization of circ_0000629 in T24 and SW780 cells by the fractionation and export assay and FISH experiments. Integrated microarray analyses and bioinformatics website prediction were utilized to screen out the downstream microRNA (miRNA)/mRNA. The effects of miR-1290 and CDC73 on BC cell growth and metastasis was verified by functional rescue experiments. In addition, mice xenografts were built to measure the effect of circ_0000629 on tumor growth in vivo.
Results:
Circ_0000629 and CDC73 were reduced, and miR-1290 was significantly overexpressed in BC tissues and cells. Moreover, circ_0000629 significantly inhibited the development and metastasis of BC cells, but further overexpression of miR-1290 or knockdown of CDC73 attenuated the inhibitory effect of circ_0000629 on BC cells. Circ_0000629 localized in the cytoplasm and regulated CDC73 expression by sponging miR-1290. Further, overexpressed circ_0000629 reduced the BC tumor growth in vivo.
Conclusion:
Circ_0000629 promotes the expression of CDC73 by competitively binding to miR-1290, thereby inhibiting the growth and metastasis of BC cells.
Insights
Circular RNA circ_0000629 inhibits bladder cancer (BC) progression by regulating the miR-1290/CDC73 axis. This finding offers a potential therapeutic target for bladder cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their regulatory roles in various cancers, including bladder cancer (BC).
- The specific function and mechanism of the newly identified circ_0000629 in BC remain largely undetermined.
- This study investigates the role of circ_0000629 in BC pathogenesis.
Purpose of the Study:
- To elucidate the functional role of circ_0000629 in bladder cancer.
- To identify the underlying molecular mechanism by which circ_0000629 influences BC progression.
- To evaluate circ_0000629 as a potential therapeutic target for BC.
Main Methods:
- Analysis of circRNA expression data from public databases (GSE147985, GSE92675) and clinical samples.
- Overexpression of circ_0000629 in BC cell lines (T24, SW780) to assess effects on proliferation, apoptosis, and metastasis.
- Subcellular localization studies using fractionation and FISH assays.
- Bioinformatic analysis to predict miRNA/mRNA interactions.
- Functional rescue experiments and in vivo mouse xenograft models to validate findings.
Main Results:
- Circ_0000629 and CDC73 expression were decreased, while miR-1290 was upregulated in BC tissues and cells.
- Overexpression of circ_0000629 suppressed BC cell proliferation and metastasis.
- Circ_0000629 acts as a sponge for miR-1290, thereby upregulating CDC73 expression.
- In vivo studies confirmed that circ_0000629 inhibits tumor growth in mice.
Conclusions:
- Circ_0000629 functions as a tumor suppressor in bladder cancer.
- The mechanism involves circ_0000629 sponging miR-1290 to promote CDC73 expression.
- Circ_0000629 holds potential as a therapeutic target for bladder cancer treatment.
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