{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["30"],"submitter":["Soni D"],"pubmed_abstract":["Risks of radiation exposure necessitate the development of radioprophylactic drugs. We have reported the efficacy of CDX-301, a recombinantly developed human protein form of Fms-related tyrosine kinase 3 ligand (Flt3L), as a radioprophylactic and radiomitigatory agent. Here, we performed global microRNA profiling to further understand the mechanism of action of CDX-301. We find that CDX-301 administration 24 h prior to total body irradiation prevents radiation-induced dysregulation of microRNA biogenesis and expression in murine serum and spleen samples in a time- and tissue-dependent manner. Further analysis shows that activation of the HOTAIR regulatory pathway has a prominent function in radiation-induced injury responses, which is inhibited by pre-treatment with CDX-301. Moreover, CDX-301 attenuates radiation-induced dysregulation of several cellular functions such as inflammatory and immune responses. In corroboration, we also find that pre-treatment with CDX-301 restores the expression of bone marrow aplasia markers and inflammatory cytokines and growth factors, as well as the expression of genes associated with MAP kinase and TGF-β pathways that are altered by radiation. Our findings provide new insights into CDX-301-mediated molecular and cellular mechanisms and point to a possible novel radioprotective drug for the prevention of irradiation-induced injury and hematopoietic acute radiation syndrome. Graphical abstract  This study identifies that CDX-301 averts radiation-induced lethal responses through prevention of dysregulated microRNA biogenesis, inhibition of HOTAIR regulatory pathway and Flt3L, and attenuation of dysregulated cellular functions, thus providing new insights into CDX-301-mediated molecular and cellular mechanisms and pointing to a possible novel radioprotective drug for hematopoietic acute radiation syndrome."],"journal":["Molecular therapy. Nucleic acids"],"pagination":["569-584"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9703457"],"repository":["biostudies-literature"],"pubmed_title":["CDX-301 prevents radiation-induced dysregulation of miRNA expression and biogenesis"],"pmcid":["PMC9703457"],"pubmed_authors":["Kumar V","Thomas L","Ghosh S","Biswas S","Bhattacharyya S","Soni D","Holmes-Hampton G","Biswas R"],"additional_accession":[]},"is_claimable":false,"name":"CDX-301 prevents radiation-induced dysregulation of miRNA expression and biogenesis","description":"Risks of radiation exposure necessitate the development of radioprophylactic drugs. We have reported the efficacy of CDX-301, a recombinantly developed human protein form of Fms-related tyrosine kinase 3 ligand (Flt3L), as a radioprophylactic and radiomitigatory agent. Here, we performed global microRNA profiling to further understand the mechanism of action of CDX-301. We find that CDX-301 administration 24 h prior to total body irradiation prevents radiation-induced dysregulation of microRNA biogenesis and expression in murine serum and spleen samples in a time- and tissue-dependent manner. Further analysis shows that activation of the HOTAIR regulatory pathway has a prominent function in radiation-induced injury responses, which is inhibited by pre-treatment with CDX-301. Moreover, CDX-301 attenuates radiation-induced dysregulation of several cellular functions such as inflammatory and immune responses. In corroboration, we also find that pre-treatment with CDX-301 restores the expression of bone marrow aplasia markers and inflammatory cytokines and growth factors, as well as the expression of genes associated with MAP kinase and TGF-β pathways that are altered by radiation. Our findings provide new insights into CDX-301-mediated molecular and cellular mechanisms and point to a possible novel radioprotective drug for the prevention of irradiation-induced injury and hematopoietic acute radiation syndrome. Graphical abstract  This study identifies that CDX-301 averts radiation-induced lethal responses through prevention of dysregulated microRNA biogenesis, inhibition of HOTAIR regulatory pathway and Flt3L, and attenuation of dysregulated cellular functions, thus providing new insights into CDX-301-mediated molecular and cellular mechanisms and pointing to a possible novel radioprotective drug for hematopoietic acute radiation syndrome.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-04T19:37:47.626Z","creation":"2025-04-04T19:37:47.626Z"},"accession":"S-EPMC9703457","cross_references":{}}