Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

Abstract

Circular RNAs (circRNAs), a class of new endogenous non-coding RNAs (ncRNAs), are closely related to the carcinogenic process and play a critical role in tumor metastasis. CircRNAs can lay the foundation for tumor metastasis via promoting tumor angiogenesis, make tumor cells gain the ability of migration and invasion by regulating epithelial-mesenchymal transition (EMT), interact with immune cells, cytokines, chemokines, and other non-cellular components in the tumor microenvironment, damage the normal immune function or escape the immunosuppressive network, and further promote cell survival and metastasis. Herein, based on the characteristics and biological functions of circRNA, we elaborated on the effect of circRNA via circRNA-associated competing endogenous RNA (ceRNA) network by acting as miRNA/isomiR sponges on tumor angiogenesis, cancer cell migration and invasion, and interaction with the tumor microenvironment (TME), then explored the potential interactions across different RNAs, and finally discussed the potential clinical value and application as a promising biomarker. These results provide a theoretical basis for the further application of metastasis-related circRNAs in cancer treatment. In summary, we briefly summarize the diverse roles of a circRNA-associated ceRNA network in cancer metastasis and the potential clinical application, especially the interaction of circRNA and miRNA/isomiR, which may complicate the RNA regulatory network and which will contribute to a novel insight into circRNA in the future.

Analysis of infiltrated immune cells in left atriums from patients with atrial fibrillation and identification of circRNA biomarkers for postoperative atrial fibrillation

“…MiRNAs are noncoding RNAs with length of 21-24 nucleotide and mediate gene expression by binding to the 3′-untranslated region of mRNA which inhibits mRNA translation or inducing mRNA degradation (Blazejowska et al, 2021). CircRNAs, new type of endogenous non-coding RNAs can form covalent closed-loop structures through reverse splicing with longer half-life than mRNA (Guo et al, 2022). Both of miRNAs and circRNAs involve in the development and progression of cardiac diseases and might be potential biomarkers for cardiac diseases (Lu et al, 2022).…”

CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease

“…CircZXDC is a circular form of the ZXD family zinc finger C (ZXDC) gene [ 33 , 34 ], and its function is still unclear. Current knowledge of circRNA has characterized it as noncoding RNA, and an increasing number of circRNAs have been found to be associated with pretranscription/post-transcription processes by acting as miRNA sponges, protein decoys, splicing regulators, and transcription and chromatin modifiers [ 35 , 36 , 37 ]. Because of the characteristics of circRNA, including its stable structure due to its covalently closed loops [ 38 ], redundant expression level, and easy detection, it is currently considered an optimal diagnostics biomarker for various diseases [ 39 , 40 , 41 ].…”

Mechanism underlying circRNA dysregulation in the TME of digestive system cancer

“…Most of circRNAs involved in this review can regulate downstream targets by acting as miRNA sponges to affect the TME in digestive system cancers. Although circRNA has a unique closed-loop structure, it still contains miRNA binding sites, which endows it with potential as a miRNA sponge (60)(61)(62). This property suggests that circRNAs can inhibit the activity of mature miRNAs, increase the level of endogenous targets, and inhibit miRNAs to regulate the expression of downstream genes (63,64).…”