{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent clinical investigations have revealed that altered expression levels of microRNA‐4485 (miR‐4485) may serve as potential biomarkers in neuropsychiatric disorders. In patients with major depressive disorder (MDD), a panel of miRNAs—including miR‐4485—was found to be significantly up‐regulated in peripheral blood mononuclear cells, and bioinformatic analyses highlighted enrichment in pathways controlling nervous system and brain functions. These results support the view that miR‐4485 could be involved in the molecular pathogenesis of MDD and serve as a useful diagnostic indicator."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of mitochondrial regulation, miR‐4485 has been shown to translocate into mitochondria, where it directly binds mitochondrial 16S rRNA. This interaction modulates the processing of precursor rRNA at the 16S rRNA–ND1 junction and affects the translation of downstream transcripts. The resulting alterations in mitochondrial complex I activity, ATP production, reactive oxygen species (ROS) levels, and apoptosis contribute to an antitumor effect in breast carcinoma cells, positioning miR‐4485 as a candidate tumor suppressor through its regulation of mitochondrial RNA processing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in mitochondrial function, miR‐4485 appears to impact bone homeostasis. In COVID‐19 patients, the up‐regulation of miR‐4485 was found to negatively regulate osteogenic differentiation. Functional studies identified toll‐like receptor 4 (TLR‐4) as a potential target through which miR‐4485 suppresses osteoblastic activity, suggesting that elevated miR‐4485 levels may contribute to impaired fracture healing and represent a promising target for therapeutics aimed at preventing osteoporosis in affected individuals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn reproductive biology, differential expression of miR‐4485 has been implicated in idiopathic asthenozoospermia—a condition characterized by reduced sperm motility. Down‐regulation of miR‐4485‐3p in spermatozoa was associated with mitochondrial dysfunction, with bioinformatic analysis identifying key targets (including DNAH1, KIT, and PARK7) that have established roles in sperm structure and function. This finding underscores miR‐4485’s potential involvement in modulating mitochondrial integrity in the context of male infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary studies in cardiovascular research have investigated mitochondrial regulatory pathways distinct from those mediated by miR‐4485. In a model of ischemic heart failure, down‐regulation of the methyltransferase‐like protein METTL13 was shown to impair mitochondrial function by destabilizing c‐Cbl and, in turn, reducing SERCA2a expression essential for calcium handling. Although this work does not directly involve miR‐4485, it highlights the broader importance of mitochondrial RNA and protein processing in maintaining cellular homeostasis and cardiac contractile function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, studies examining testicular function have focused on FEAT, the protein product of METTL13, showing its expression in Leydig cells and its role in facilitating insulin‐like factor 3 (INSL3) production, which is critical for testicular descent. While these findings are centered on epigenetic and post‐translational modifications mediated by METTL13/FEAT rather than miR‐4485 per se, they further illustrate the complexity of RNA‐mediated regulation and mitochondrial involvement across diverse physiological systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}]}]}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hui-min Fan, Xin-yang Sun, Wei Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of microRNA in peripheral blood mononuclear cells as specific biomarker for major depressive disorder patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Psychiatr Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpsychires.2014.08.007"}], "href": "https://doi.org/10.1016/j.jpsychires.2014.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25201637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25201637"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lakshmi Sripada, Kritarth Singh, Anastasiya V Lipatova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hsa-miR-4485 regulates mitochondrial functions and inhibits the tumorigenicity of breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-017-1517-5"}], "href": "https://doi.org/10.1007/s00109-017-1517-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28220193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28220193"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Bobin Mi, Yuan Xiong, Chenming Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.56657"}], "href": "https://doi.org/10.7150/ijbs.56657"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33867845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33867845"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zohreh Heidary, Majid Zaki-Dizaji, Kioomars Saliminejad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-4485-3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Andrologia (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/and.13539"}], "href": "https://doi.org/10.1111/and.13539"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32030798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32030798"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shuting Yu, ZhiYong Sun, Xiuzhu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mettl13 protects against cardiac contractile dysfunction by negatively regulating C-Cbl-mediated ubiquitination of SERCA2a in ischemic heart failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci China Life Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11427-022-2351-1"}], "href": "https://doi.org/10.1007/s11427-022-2351-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37450238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37450238"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yan Li, Kyosuke Kobayashi, Kosho Murayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FEAT enhances INSL3 expression in testicular Leydig cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12644"}], "href": "https://doi.org/10.1111/gtc.12644"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30178547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30178547"}]}]}]}