{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn a wide spectrum of malignancies, MIR501 exhibits context‐dependent functions that appear to be isoform‐specific. In gastrointestinal cancers such as gastric and colorectal cancer, the MIR501‐5p isoform is frequently overexpressed, where it enhances cell proliferation, migration, invasion and chemoresistance through repression of tumor suppressors such as BLID, LPAR1 and ERRFI1, while in colorectal cancer MIR501‐3p promotes proliferation by targeting APC. In hepatocellular carcinoma conflicting roles have been reported; on one hand, MIR501 upregulation facilitates invasion and epithelial–mesenchymal transition by targeting JDP2, whereas in other studies decreased MIR501‐3p levels are associated with metastasis suppression via inhibition of LIN7A. In pancreatic ductal adenocarcinoma, elevated levels of MIR501‐3p—either within tumors or delivered via tumor‐associated macrophage exosomes—correlate with increased invasiveness (likely through downregulation of adhesion molecules such as E–cadherin). In addition, reduced MIR501‐3p expression in prostate cancer, non–small cell lung cancer and glioma contributes to tumor cell proliferation and chemoresistance, with its restoration suppressing growth through targeting factors including CREPT, RAP1A and MYCN. Moreover, in osteosarcoma, aberrant overexpression of MIR501‐3p not only enhances tumor cell proliferation but also promotes osteoclastogenesis via modulation of the PTEN/PI3K/Akt cascade, and in ovarian cancer, sequestration of MIR501‐3p by LINC00452 appears to relieve repression of ROCK1. Finally, initial investigations in endometrial cancer point to a yet‐to‐be–clarified role for MIR501 in tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, MIR501 plays significant roles in other disease settings. In autosomal dominant polycystic kidney disease, upregulation of MIR501‐5p represses the expression of PTEN and TSC1, thereby stimulating mTOR signaling, which intensifies cell proliferation via subsequent attenuation of p53‐dependent apoptosis. Similarly, in sepsis–induced myocardial dysfunction, reduced MIR501‐5p levels are associated with heightened cardiomyocyte apoptosis and compromised cardiac performance, whereas restoring its levels improves functional parameters through targeting NR4A3. Furthermore, emerging data from studies in congenital hydrocephalus indicate that dysregulation of exosomal MIR501 in cerebrospinal fluid may contribute to disease pathology, although its precise role in this neurological disorder remains to be firmly established."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its functions in disease pathogenesis, MIR501 is implicated in fundamental immune and developmental processes. In lymphoid cells, MIR501 directly regulates the expression of RAG1, thereby modulating V(D)J recombination with potential implications for immunoglobulin gene rearrangements and leukemogenesis. Recent human studies also associate MIR501‐3p with cognitive performance, underscoring its roles in maintaining neuronal integrity and synaptic plasticity, while investigations in skeletal muscle point to its involvement in modulating progenitor cell function during age–related muscle regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jiang Jin, Shanhong Tang, Lin Xia, et al. 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