Liao, Keng-MaoKeng-MaoLiaoHsu, Wei-LunWei-LunHsuHuang, Wan-YiWan-YiHuangLuo, Wei-JiaWei-JiaLuoChang, Jung-HsuanJung-HsuanChangSUNG-LIANG YUPAN-CHYR YANGKANG-YI SU2025-09-042025-09-042025-07-01https://scholars.lib.ntu.edu.tw/handle/123456789/731780Background: Brain-enriched miR-137 is highly associated with neuropsychiatric disorders and neural development. Although complete loss of miR-137 that leads to postnatal lethality had been addressed in mice, the underlying mechanism particularly related to growth and development remains unknown. Results: MiR-137-deficient mice (Mir137−/−) exhibited postnatal lethality, severe growth retardation, osteoporosis, fat atrophy, and hypothermia. Despite comparable serum growth hormone (GH) levels, IGF-1 levels in both liver and serum were significantly reduced, with compensatory upregulation of IGF-1 receptor expression in major organs. Reduced IGF-1 levels were not due to defects in GH secretion by the pituitary nor GH responsiveness of hepatocytes. Instead, impaired in vivo GH-induced p-STAT5 signaling suggested GH resistance in Mir137−/−. Conditional deletion of Mir137 in the nervous system, but not in the liver, showed similar results, confirming the brain-specific role of miR-137. Transcriptomic analyses revealed that differentially expressed genes in the brain were enriched in development and neurogenesis while those in the liver showed diverse and less enrichments. IGF-1 reduction caused by miR-137 deficiency emerged as a central factor impacting the cell proliferation network to systemic growth. Conclusions: This study underscores the critical role of miR-137 in failure to thrive through regulation of the GH/IGF-1 axis and supports the use of MiR137−/− as a disease model for GH resistance. Given the conserved miR-137 sequences between mice and humans, further human studies or clinical trials may validate its potential as a biomarker and therapeutic target for growth retardation.enGH resistanceGrowth retardationIGF-1Knockout miceMiR-137[SDGs]SDG3journal article10.1186/s12915-025-02306-840598150