Crosstalk between circRNAs and the MAPK signaling pathway in cancer progression

Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small ncRNAs, play critical roles in regulating biological processes and disease development. Among these, circRNAs, characterized by their single-stranded, covalently closed structures, act as protein templates, microRNA sponges, and transcriptional regulators, exhibiting high stability and distinct expression profiles. CircRNAs play an important role in several diseases, including autoimmune disorders, cardiovascular diseases, neurological conditions, and cancers. In cancer, they influence key mechanisms like cell cycle development, angiogenesis, apoptosis, proliferation, motility, and metastasis. Meanwhile, the mitogen-activated protein kinase (MAPK) signaling pathways—especially the Ras/Raf/MEK/ERK cascade—are central to controlling cell survival, proliferation, and tumor development, with hyperactivation of ERK linked to cancer progression. Despite the important roles of both circRNAs and MAPK pathways in oncogenesis, the mechanisms underlying their interplay remain poorly understood. This review aims to fill this knowledge gap by examining the bidirectional interactions between circRNAs and MAPK signaling in cancer and explores therapeutic implications, focusing on strategies such as circRNA modulation (targeting their functions as transcriptional regulators or microRNA sponges) and MAPK pathway inhibition to control cancer progression.