circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune

Roberta Piras1, Emily Y Ko1, Connor Barrett2

  • 1Department of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Nature Communications
|November 26, 2022
PubMed

Insights

Circular RNAs (circRNAs) in soft tissue sarcoma promote tumor growth by creating a pro-tumor microenvironment. Targeting specific circRNAs may enhance anti-tumor immune responses and improve cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Exonic circular RNAs (circRNAs) are non-coding RNA species found in tumors.
  • The functional role of circRNAs in cancer progression, particularly in soft tissue sarcoma, remains largely unknown.

Purpose of the Study:

  • To identify circRNAs in soft tissue sarcoma cells.
  • To investigate the role of circRNAs in regulating sarcoma growth in vivo.
  • To explore the mechanisms by which circRNAs influence the tumor microenvironment.

Main Methods:

  • Profiling of circRNAs expressed in soft tissue sarcoma cells.
  • In vivo studies to assess the impact of specific circRNAs (circCsnk1g3, circAnkib1) on tumor growth.
  • Analysis of gene expression related to immune response and inflammation.
  • Investigation of the RIG-I pathway in circRNA-mediated regulation.

Main Results:

  • circCsnk1g3 and circAnkib1 were identified as promoters of sarcoma growth.
  • These circRNAs shape a pro-tumorigenic microenvironment by regulating extrinsic tumor-promoting elements.
  • circCsnk1g3 and circAnkib1 control interferon-related genes and pro-inflammatory factors, influencing immune cell recruitment and activation.
  • Mechanistically, circRNAs may repress pro-inflammatory elements by buffering RIG-I pathway activation.

Conclusions:

  • Specific circRNAs, circCsnk1g3 and circAnkib1, play a significant role in soft tissue sarcoma progression.
  • These circRNAs modulate the tumor microenvironment and immune responses.
  • Targeting these circRNAs presents a potential therapeutic strategy to enhance anti-tumor immunity and treatment efficacy.

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