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

Abstract

Cancer is a multifactorial disease and wealth of information has enabled basic and clinical researchers to develop a better conceptual knowledge of highly heterogeneous nature of cancer. Deregulations of spatiotemporally controlled transduction pathways played 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. Significance StatementRecently, many researchers have focused on the NRF2-driven signaling in cancer progression. Excitingly, discovery of non-coding RNAs has added new layers of intricacy to already complicated nature of KEAP1/NRF2 signaling in different cancers. These interactions are shaping the NRF2-driven signaling landscape and better knowledge of these pathways will be advantageous in pharmacological modulation of non-coding RNA-mediated NRF2 signaling in various cancers. Introduction:Nuclear factor erythroid 2-related factor 2(NRF2) is a master transcriptional regulator. NRF2 contextually integrates cellular stress signals and responds by regulation of myriad of transcriptional networks. NRF2 sequestration is regulated by an inhibitory molecule, Kelch-like ECH-associated protein-1 (KEAP1), until inducers undergo an interaction with cysteine thiol residues of KEAP1. These chemical modifications are This article has not been copyedited and formatted. The final version may differ from this version.

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