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Published on: July 20, 2019
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.
Abstract:
Exonic circular RNAs (circRNAs) produce predominantly non-coding RNA species that have been recently profiled in many tumors. However, their functional contribution to cancer progression is still poorly understood. Here, we identify the circRNAs expressed in soft tissue sarcoma cells and explore how the circRNAs regulate sarcoma growth in vivo. We show that circCsnk1g3 and circAnkib1 promote tumor growth by shaping a pro-tumorigenic microenvironment, possibly due to their capabilities to regulate tumor-promoting elements extrinsic to the tumor cells. Accordingly, circCsnk1g3 and circAnkib1 can control the expression of interferon-related genes and pro-inflammatory factors in the sarcoma cells, thus directing immune cell recruitment into the tumor mass, and hence their activation. Mechanistically, circRNAs may repress pro-inflammatory elements by buffering activation of the pathways mediated by RIG-I, the cytosolic viral RNA sensor. The current findings suggest that the targeting of specific circRNAs could augment the efficacy of tumor and immune response to mainstay therapies.
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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