Circular RNA serves as an upstream regulator of the miRNA//ABCC1 axis in human cancers

Multidrug resistance (MDR) is one of the main causes of chemotherapy failure and cancer recurrence. Among the ATP-binding cassette (ABC) transporter family, ATP binding cassette subfamily C member 1 (ABCC1/MRP1) is a key member that significantly reduces intracellular drug accumulation by effluxing various chemotherapeutic drugs, leading to treatment failure. Recent studies have found that microRNA (miRNA) can inhibit ABCC1 expression at the post-transcriptional level by targeting its 3' untranslated region (3'-UTR) region, thereby affecting chemotherapy sensitivity. However, miRNA itself is regulated by upstream molecules, particularly circular RNA (circRNA), which acts as competing endogenous RNA (ceRNA) and can bind miRNA through the sponge mechanism, relieving their inhibition of ABCC1 and promoting the MDR phenotype. Multiple studies have identified specific circRNA/miRNA/ABCC1 regulatory axes in various cancers such as non-small cell lung cancer, colorectal cancer, breast cancer, and ovarian cancer. This axis is not only involved in chemotherapy resistance but also affects tumor proliferation, migration, and invasion. Due to their high stability and tissue specificity, circRNAs and miRNAs have the potential as liquid biopsy biomarkers and therapeutic targets. Despite challenges posed by the complexity of the ceRNA network, intervention strategies targeting this axis, such as circRNA knockdown or miRNA mimics, are still considered important approaches to reverse cancer MDR. In addition, emerging computational approaches, such as graph learning, hypergraph networks, and pre-trained models, now enable large-scale prediction of circRNA-miRNA interactions, offering powerful tools to further dissect the regulatory axes underlying MDR.