TY - JOUR
T1 - circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment
AU - Piras, Roberta
AU - Ko, Emily Y.
AU - Barrett, Connor
AU - De Simone, Marco
AU - Lin, Xianzhi
AU - Broz, Marina T.
AU - Tessaro, Fernando H.G.
AU - Castillo-Martin, Mireia
AU - Cordon-Cardo, Carlos
AU - Goodridge, Helen S.
AU - Di Vizio, Dolores
AU - Batish, Mona
AU - Lawrenson, Kate
AU - Chen, Y. Grace
AU - Chan, Keith Syson
AU - Guarnerio, Jlenia
N1 - Funding Information:
J.G. was supported by the K99/R00 grant (CA212200) and R01 (CA258265) for the execution of this work. Additionally, this work was supported by grants from the Sarcoma Foundation of America (grant 2019 SFA 15–19), Tower Cancer Research Foundation, and the Margaret Early Medical Research Trust to J.G. Mona Batish was supported by NIH grant DP5 OD012160. Schematic representations were prepared with Biorender ( www.biorender.com ).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-022-34872-8
DO - 10.1038/s41467-022-34872-8
M3 - Article
C2 - 36433954
AN - SCOPUS:85142502523
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7243
ER -