Статья

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

Roberta PirasDepartment of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAEmily KoDepartment of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAConnor BarrettDepartment of Medical and Molecular Sciences, University of Delaware, Newark, DE, USAMarco De SimoneDepartment of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAXianzhi LinDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USAMarina T. BrozDepartment of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAFernando Henrique Galvão TessaroDepartment of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAMireia Castillo-MartínDepartment of Pathology, Mount Sinai School of Medicine, The Mount Sinai Medical Center, New York, NY, 10029, USACarlos Cordon‐CardoDepartment of Pathology, Mount Sinai School of Medicine, The Mount Sinai Medical Center, New York, NY, 10029, USAHelen S. GoodridgeBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USADolores Di VizioDepartment of Surgery and Department of Pathology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAMona BatishDepartment of Medical and Molecular Sciences, University of Delaware, Newark, DE, USAKate LawrensonCenter for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAY. Grace ChenDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USAKeith Syson ChanDepartment of Pathology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAJlenia GuarnerioBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [email protected]

2022en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1038/s41467-022-34872-8

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar