{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSeveral studies have examined diverse regulatory pathways in different tissues. For example, work on transmembrane adaptor molecules such as TRIM has shown that, although these proteins participate in modulating T‐cell receptor signaling, they are largely dispensable for T‐cell development and peripheral immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, independent investigations into steroid 5α‐reductase type 2 (SRD5A2) have highlighted its relevance in disorders of the male reproductive system. In benign prostatic hyperplasia, for instance, altered expression of SRD5A2 correlates with the variability in patients’ responses to 5α‐reductase inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBuilding on this body of work, a recent study has delineated a critical role for miR-1199-5p in the context of hypospadias. Here, experimental approaches including dual-luciferase reporter assays demonstrated that miR-1199-5p directly targets SRD5A2, acting as an upstream posttranscriptional regulator. In primary cells from hypospadias patients, a significant downregulation of miR-1199-5p was observed alongside an upregulation of SRD5A2. This imbalance leads to increased cell proliferation, migration, invasion, and the promotion of epithelial-to-mesenchymal transition—all of which contribute to the abnormal cellular phenotypes characteristic of hypospadias."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings indicate that miR-1199-5p plays a decisive role in safeguarding normal epithelial cell behavior by ensuring appropriate levels of SRD5A2. The miR-1199-5p/SRD5A2 regulatory axis emerges as a promising therapeutic target for correcting cellular dysregulation in hypospadias, broadening our understanding of microRNA-mediated control in contexts beyond immune signaling.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Uwe Kölsch, Börge Arndt, Dirk Reinhold, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Normal T-cell development and immune functions in TRIM-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.9.3639-3648.2006"}], "href": "https://doi.org/10.1128/MCB.26.9.3639-3648.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16612002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16612002"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Uwe Koelsch, Burkhart Schraven, Luca Simeoni "}, {"type": "b", "children": [{"type": "t", "text": "SIT and TRIM determine T cell fate in the thymus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.9.5930"}], "href": "https://doi.org/10.4049/jimmunol.181.9.5930"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18941181"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18941181"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhanliang Liu, Zhemin Lin, Fang Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of mir-1199-5p is associated with reduced type 2 5-α reductase expression in benign prostatic hyperplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Urol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12894-022-01121-5"}], "href": "https://doi.org/10.1186/s12894-022-01121-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36344974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36344974"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yifu Chen, Jianjun Hu, Liucheng Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroR-1199-5p targeting SRD5A2 promotes the biological behavior and EMT of hypospadias cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol (Noisy-le-grand) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14715/cmb/2024.70.6.19"}], "href": "https://doi.org/10.14715/cmb/2024.70.6.19"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38836672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38836672"}]}]}]}