Roles of circRNAs in regulating the tumor microenvironment

Abstract

CircRNAs, a type of non-coding RNA widely present in eukaryotic cells, have emerged as a prominent focus in tumor research. However, the functions of most circRNAs remain largely unexplored. Known circRNAs exert their regulatory roles through various mechanisms, including acting as microRNA sponges, binding to RNA-binding proteins, and functioning as transcription factors to modulate protein translation and coding. Tumor growth is not solely driven by gene mutations but also influenced by diverse constituent cells and growth factors within the tumor microenvironment (TME). As crucial regulators within the TME, circRNAs are involved in governing tumor growth and metastasis. This review highlights the role of circRNAs in regulating angiogenesis, matrix remodeling, and immunosuppression within the TME. Additionally, we discuss current research on hypoxia-induced circRNAs production and commensal microorganisms’ impact on the TME to elucidate how circRNAs influence tumor growth while emphasizing the significance of modulating the TME.

Hallmarks of cancer resistance

“…CircRNAs contribute to the crosstalk between cancer cells and the surrounding stroma, establishing a supportive niche that promotes resistance. 250 Their influence extends to the regulation of EMT and the promotion of metastatic potential, further complicating therapeutic interventions. 251 Dysregulation of specific circRNAs are linked with the development of drug resistance, affecting key cellular processes such as apoptosis, DNA repair, and cell cycle regulation.…”

Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes

“…Functions of circRNAs include sequestration of proteins, sponging of microRNAs, transcription regulation and production of novel proteins [13][14][15][16] . CircRNAs are associated with a growing number of pathological conditions and offer novel avenues for diagnosis and therapy [17][18][19] .…”

Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes

“…Functions of circRNAs include sequestration of proteins, sponging of microRNAs, transcription regulation and production of novel proteins 13 – 16 . CircRNAs are associated with a growing number of pathological conditions and offer novel avenues for diagnosis and therapy 17 – 19 .…”