Department of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Medical and Molecular Sciences, University of Delaware, Newark, DE, USA.
Nat Commun. 2022 Nov 25;13(1):7243. doi: 10.1038/s41467-022-34872-8.
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.
外显子环状 RNA（circRNAs）主要产生非编码 RNA 种类，这些 RNA 已在许多肿瘤中得到了广泛研究。然而，它们对癌症进展的功能贡献仍知之甚少。在这里，我们鉴定了软组织肉瘤细胞中表达的 circRNAs，并探讨了它们如何在体内调节肉瘤的生长。我们发现 circCsnk1g3 和 circAnkib1 通过塑造促肿瘤微环境促进肿瘤生长，这可能是由于它们能够调节肿瘤细胞外的肿瘤促进因子。因此，circCsnk1g3 和 circAnkib1 可以控制肉瘤细胞中干扰素相关基因和促炎因子的表达，从而将免疫细胞募集到肿瘤块中，并激活它们。从机制上讲，circRNAs 可以通过缓冲由细胞质病毒 RNA 传感器 RIG-I 介导的途径的激活来抑制促炎因子。这些发现表明，针对特定的 circRNAs 可以增强肿瘤和免疫对主流治疗方法的反应效果。
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