A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking

Emily B Harrison1,2, Alessandro Porrello1, Brittany M Bowman1

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.

Cancer Research
|September 26, 2020
PubMed

Insights

MicroRNA-671-5p inhibits lung squamous cell carcinoma (LUSC) metastasis by targeting the CDR1as/CDR1 axis. This axis promotes cancer cell migration and Golgi trafficking, offering a new therapeutic target for LUSC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Lung squamous cell carcinoma (LUSC) is a metastatic cancer with poor patient outcomes.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
  • The function of CDR1as and its associated transcript CDR1 in LUSC metastasis is not well understood.

Purpose of the Study:

  • To investigate the role of the miR-671-5p/CDR1as/CDR1 axis in LUSC metastasis.
  • To identify novel therapeutic targets for reducing LUSC metastasis.

Main Methods:

  • Integrated screening approach to identify regulatory interactions.
  • Analysis of microRNA (miRNA) and circRNA functions in LUSC cells.
  • Investigation of protein interactions and cellular trafficking pathways.
  • In vivo studies using therapeutic inhibition of the identified axis.

Main Results:

  • miR-671-5p inhibits LUSC metastasis by targeting the CDR1as/CDR1 axis.
  • CDR1, the antisense transcript of CDR1as, promotes LUSC cell migration and metastasis.
  • CDR1 interacts with AP1 and COPI proteins, influencing Golgi trafficking.
  • Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced LUSC metastasis in vivo.

Conclusions:

  • The circRNA CDR1as/CDR1 axis plays a significant role in promoting LUSC metastasis and Golgi trafficking.
  • miR-671-5p acts as a tumor suppressor by inhibiting this axis.
  • The CDR1as/CDR1 axis represents a novel therapeutic target for LUSC.

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