{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent findings in gastric cancer have identified that the long non‐coding RNA NORAD, upregulated under oxidative stress by oxaliplatin treatment, can enhance autophagy flux in resistant cells by sponging miR-433-3p. In this setting, miR-433-3p normally would act to limit the stability of the ATG5-ATG12 complex; however, its sequestration by NORAD results in the positive regulation of this complex, thereby promoting autophagy and reducing oxidative stress. This mechanism contributes to the development of oxaliplatin resistance, making miR-433-3p a potential target for overcoming chemoresistance in gastric cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, studies investigating RNA-binding proteins in neuronal cells—such as those examining the Jerky protein—have focused on the roles of these proteins in mRNA and DNA interactions, ribosome assembly, and cellular stress responses. Although these studies (using mouse models of epilepsy) underscored how RNA binding and processing might influence cellular survival and stress pathways, they did not specifically implicate miR-433-3p or a similar MIR4330 mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, research into the human orthologue of the mouse jerky gene delineated its dynamic nuclear localization and association with centromeric regions and PML nuclear bodies throughout the cell cycle. These findings elaborate on the broader context of RNA/DNA binding proteins in cellular regulation but did not extend to the modulation of autophagy or chemoresistance via miR-433-3p. Consequently, while the Jerky studies expand our understanding of RNA-mediated regulation in different cellular contexts, the oncologic role of miR-433-3p appears to be distinct and specific to NORAD-mediated autophagy in the setting of oxaliplatin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jizhao Wang, Yuchen Sun, Xing Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidative stress activates NORAD expression by H3K27ac and promotes oxaliplatin resistance in gastric cancer by enhancing autophagy flux via targeting the miR-433-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-03368-y"}], "href": "https://doi.org/10.1038/s41419-020-03368-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33462197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33462197"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wencheng Liu, Jeremy Seto, Etienne Sibille, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNA binding domain of Jerky consists of tandemly arranged helix-turn-helix/homeodomain-like motifs and binds specific sets of mRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.12.4083-4093.2003"}], "href": "https://doi.org/10.1128/MCB.23.12.4083-4093.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12773553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12773553"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "R Waldron, T Moore "}, {"type": "b", "children": [{"type": "t", "text": "Complex regulation and nuclear localization of JRK protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST0320920"}], "href": "https://doi.org/10.1042/BST0320920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15506925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15506925"}]}]}]}