{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have highlighted the fundamental importance of RNA regulatory molecules in diverse biological contexts. For example, in mammalian neurons, the zinc finger RNA binding protein (ZFR) is an integral component of RNA granules where it interacts with Staufen2 to facilitate early mRNA transport and localization to distinct synaptic sites, a process essential for synaptic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, investigation of Zfr expression during early development in mouse, zebrafish, and nematode models demonstrates a dynamic, maternally contributed expression pattern and underscores its critical role in nuclear localization events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, studies in colorectal and liver cancer models reveal that aberrant overexpression of ZFR accelerates tumor cell proliferation, positioning it as a potential oncogene in these digestive system malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin this broader framework of RNA-mediated regulation, a distinct non-coding RNA—miR-4755-5p—has recently been identified as a key player in chemoresistance. In a decitabine (5-aza-2′-deoxycytidine)–resistant human leukemia model, extracellular vesicles and particles (EVPs) derived from DAC-resistant KG1a cells were found to be enriched in miR-4755-5p. When delivered to sensitive cells, miR-4755-5p directly targets the cyclin-dependent kinase inhibitor CDKN2B, dampening its expression and thereby promoting cell cycle progression and drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings illustrate a multifaceted landscape in which RNA-binding proteins like ZFR regulate RNA localization and gene expression in both normal and pathological states, while non‐coding RNAs such as miR-4755-5p emerge as crucial modulators of cellular responses to therapeutic agents. In particular, the ability of miR-4755-5p to confer resistance to decitabine through targeted inhibition of key cell cycle regulators not only deepens our understanding of drug resistance mechanisms but also identifies a promising target for overcoming chemotherapeutic failure.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "George Elvira, Bernard Massie, Luc DesGroseillers "}, {"type": "b", "children": [{"type": "t", "text": "The zinc-finger protein ZFR is critical for Staufen 2 isoform specific nucleocytoplasmic shuttling in neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2005.03523.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2005.03523.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16277607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16277607"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Canan Doğanlı, Tine Kjærgaard, Anders Olsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early developmental expression of Mus musculus zinc finger RNA-binding protein compared to orthologs in Caenorhabditis elegans and Danio rerio and subcellular localization of Mus musculus and Caenorhabditis elegans zinc finger RNA-binding protein in 2-cell Mus musculus embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2010.1085"}], "href": "https://doi.org/10.1089/dna.2010.1085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21091219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21091219"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yanrong Long, Teresa A Marian, Zhubo Wei "}, {"type": "b", "children": [{"type": "t", "text": "ZFR promotes cell proliferation and tumor development in colorectal and liver cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.04.103"}], "href": "https://doi.org/10.1016/j.bbrc.2019.04.103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31010678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31010678"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lei Lei, Yi Wang, Rui Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transfer of miR-4755-5p through extracellular vesicles and particles induces decitabine resistance in recipient cells by targeting CDKN2B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.23521"}], "href": "https://doi.org/10.1002/mc.23521"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36825759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36825759"}]}]}]}