Interplay between Non-Coding RNAs and NRF2 in Different Cancers: Spotlight on MicroRNAs and Long Non-Coding RNAs

Cancer is a multifactorial disease, and a wealth of information has enabled basic and clinical researchers to develop a better conceptual knowledge of the highly heterogeneous nature of cancer. Deregulations of spatio-temporally controlled transduction pathways play a central role in cancer progression. NRF2-driven signaling has engrossed significant attention because of its fundamentally unique features to dualistically regulate cancer progression. Context-dependent diametrically opposed roles of NRF2-induced signaling are exciting. More importantly, non-coding RNA (ncRNA) mediated regulation of NRF2 and interplay between NRF2 and ncRNAs have added new layers of complexity to already intricate nature of NRF2 signaling. There is a gradual enrichment in the existing pool of knowledge related to interplay between microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in different cancers. However, surprisingly, there are no clues about interplay between circular RNAs and NRF2 in various cancers. Therefore, future studies must converge on the functional characterization of additional important lncRNAs and circular RNAs, which regulated NRF2-driven signaling or, conversely, NRF2 transcriptionally controlled their expression to regulate various stages of cancer.

Automated summary

Cancer is a multifactorial disease, and the dysregulation of spatio-temporally controlled transduction pathways, particularly NRF2-driven signaling, plays a central role in cancer progression. Non-coding RNA (ncRNA) mediated regulation of NRF2 and the interplay between NRF2 and ncRNAs add complexity to NRF2 signaling. The interplay between circular RNAs and NRF2 in different cancers remains unknown. Future studies should focus on characterizing the functional roles of important ncRNAs and circular RNAs in NRF2-driven signaling and cancer progression.