Yaylım İlhan, Farooqi Ammad Ahmad, Telkoparan-Akillilar Pelin, Saso Luciano
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey (I.Y.); Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan (A.A.F.); Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, Ankara, Turkey (P.T.-A.); and Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy (L.S.)
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey (I.Y.); Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan (A.A.F.); Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, Ankara, Turkey (P.T.-A.); and Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy (L.S.).
J Pharmacol Exp Ther. 2023 Jan;384(1):28-34. doi: 10.1124/jpet.121.000921. Epub 2022 Jun 6.
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. SIGNIFICANCE STATEMENT: Recently, 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 the 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.
癌症是一种多因素疾病，大量信息使基础研究人员和临床研究人员能够更好地从概念上理解癌症高度异质性的本质。时空控制的转导通路失调在癌症进展中起核心作用。NRF2驱动的信号传导因其在双重调节癌症进展方面具有根本独特的特征而备受关注。NRF2诱导信号在不同背景下呈现出截然相反的作用，这一点令人兴奋。更重要的是，非编码RNA（ncRNA）介导的NRF2调节以及NRF2与ncRNA之间的相互作用，为已然错综复杂的NRF2信号传导本质增添了新的复杂层面。在不同癌症中，与微小RNA（miRNA）和长链非编码RNA（lncRNA）之间相互作用相关的现有知识储备在逐渐丰富。然而，令人惊讶的是，在各种癌症中，关于环状RNA与NRF2之间相互作用尚无线索。因此，未来的研究必须聚焦于其他重要lncRNA和环状RNA的功能特征，这些分子要么调节NRF2驱动的信号传导，要么相反，由NRF2转录控制其表达以调节癌症的各个阶段。意义声明：最近，许多研究人员专注于NRF2驱动的信号传导在癌症进展中的作用。令人兴奋的是，非编码RNA的发现为不同癌症中已然复杂的KEAP1/NRF2信号传导本质增添了新的复杂层面。这些相互作用正在塑造NRF2驱动的信号传导格局，更好地了解这些通路将有利于对各种癌症中由非编码RNA介导的NRF2信号传导进行药理学调控。
