Abstract
Currently, it is well known that the tumor microenvironment not only provides energy support for tumor growth but also regulates tumor signaling pathways and promotes the proliferation, invasion, metastasis, and drug resistance of tumor cells. The tumor microenvironment, especially the function and mechanism of tumor-associated macrophages (TAMs), has attracted great attention. TAMs are the most common immune cells in the tumor microenvironment and play a vital role in the occurrence and development of tumors. circular RNA (circRNA) is a unique, widespread, and stable form of non-coding RNA (ncRNA), but little is known about the role of circRNAs in TAMs or how TAMs affect circRNAs. In this review, we summarize the specific manifestations of circRNAs that affect the tumor-associated macrophages and play a significant role in tumor progression. This review helps improve our understanding of the association between circRNAs and TAMs, thereby promoting the development and progress of potential clinical targeted therapies.
Highlights
Studies have demonstrated the relationship between circular RNA (circRNA) and macrophages—for example, circASAP1 can act as a competing endogenous RNA of miR-326 and miR-532-5p to mediate tumor-associated macrophages (TAMs) infiltration, and circRNA-CDR1as may be crucial for tumor tissue immunity and cell penetration, such as CD8+ T cells, activated natural killer (NK) cells, and M2 macrophages [116]. circ-ASAP1 can mediate TAM osmosis by regulating the miR-326/miR-532-5PCSF-1 pathway [117]
Mutated p53 cancer cells can be re-transformed from macrophages to TAM through miR-1246 [157], which is beneficial for anti-inflammatory immunosuppression and the increased activities of TGF-b, while it affects the expression of related circRNAs [158]
There is no evidence that circRNAs are directly related to the differentiation of tumor-associated macrophages, but some studies have shown that they can be transformed into endogenous RNA to participate in the differentiation process
Summary
With the continuous development of high-throughput sequencing, a class of covalently closed RNA molecules with extensiveness, diversity, stability, and evolutionary conservation has come into view, known as circular RNA (circRNA) [1, 2]. circRNA has a unique covalently closed loop structure and a specific tertiary structure and exhibits tissue- and developmental stage-specific expression, whichcircRNAs Interplay With TAMs plays an essential role in multiple cellular processes [3]. Regulated circRNAs play a suppressive or carcinogenic role in the initiation and progression of cancer, affecting a number of cellular functions, such as the maintenance of proliferation signals, promotion of cell migration and invasion, resistance to apoptosis, and induction of angiogenesis [48, 49].
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