The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer

Xiaotong Zhang1, Xi Liu1, Zhifei Jing1

  • 1Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China.

Cancer Gene Therapy
|February 7, 2019
PubMed

Insights

Circular RNAs (circRNAs) regulate gene expression in cancer. This study identifies circINTS4 as a microRNA sponge for miR-146b, impacting bladder cancer (BC) progression by targeting CARMA3 and influencing key signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in gene regulation within human cancers.
  • The specific functions of circRNAs and their microRNA (miRNA) sponge activities in bladder cancer (BC) are not well understood.

Purpose of the Study:

  • To investigate the role of circINTS4 as a potential miRNA sponge for miR-146b in the context of bladder cancer (BC) tumorigenesis.
  • To elucidate the molecular mechanism by which circINTS4 influences BC progression through the miR-146b/CARMA3 axis.

Main Methods:

  • Bioinformatic analysis to identify potential circRNA-miRNA interactions.
  • Quantitative expression analysis of circINTS4 and miR-146b in BC tissues and cell lines.
  • Functional assays to assess the impact of circINTS4 on cell proliferation, migration, cell cycle, and apoptosis.
  • Mechanism studies involving direct binding assays and pathway analysis (NF-kB, P38 MAPK).

Main Results:

  • CircINTS4 expression was significantly elevated in BC tissues and cell lines with low miR-146b levels.
  • CircINTS4 demonstrated regulatory control over BC cell proliferation, migration, cell cycle, and apoptosis.
  • CircINTS4 directly sponged miR-146b, thereby inhibiting miR-146b's targeting of the CARMA3 3'-UTR.
  • The circINTS4/miR-146b/CARMA3 interaction modulated the NF-kB and P38 MAPK signaling pathways in BC cells.

Conclusions:

  • The circINTS4/miR-146b/CARMA3 regulatory axis plays a significant role in bladder cancer (BC) pathogenesis.
  • This axis represents a potential novel therapeutic target for bladder cancer (BC) intervention.

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