{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐7, whose mature products are partly transcribed from the MIR7‐2 gene, is an evolutionarily conserved non‐coding RNA that plays critical roles in normal development and cell differentiation. For example, its high expression in pancreatic islet endocrine cells contributes to β‐cell maturation and function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and modulation of MIR7‐2‐derived transcripts has been harnessed to promote the differentiation of human induced pluripotent stem cells toward functional islet‐like clusters."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, miR‐7 has been shown to stimulate neural differentiation of mesenchymal stem cells, evidencing a broader role in organogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, miR‐7 generally functions as a key regulator of tumor progression, although its activity is highly context‐dependent. In several malignancies including breast"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", glioblastoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", pancreatic"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", prostate"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", melanoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and colorectal cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "), restoration of miR‐7 levels suppresses oncogenic signaling by directly targeting key molecules such as REGγ"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", components of the EGFR/PI3K/Akt and Raf/MEK/ERK pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", EGFR itself"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and other oncogenic factors like Keap1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In glioblastoma microvascular endothelial cells, miR‐7‐5p targets RAF1 to inhibit angiogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", and in lung cancer it counteracts TLR9‐mediated tumor growth by suppressing PIK3R3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Reviews emphasize its conserved regulatory capacity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", while additional studies report that miR‐7 targets HOXB5"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", VDAC1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", and KLF4—thereby modulating VEGF‐mediated angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Furthermore, loss or aberrant expression of miR‐7 (often noted as miR‐7‐2‐3p in certain tumor types) has been correlated with enhanced EMT and invasion via deregulation of TBX2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", promotion of chemoresistance in breast"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", gastric"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "and osteosarcomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", and its epigenetic silencing is implicated in dysregulation of IGF1R signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " In bladder and endometrial cancers, long non‐coding RNAs that sponge miR‐7‐2‑3p (for example, TINCR and BMPR1B‐AS1) lead to the de‐repression of mTOR or DCLK1, respectively."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": " Additionally, in colorectal carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "and thyroid cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": ", miR‐7’s regulation or misregulation of targets has been shown to influence proliferative and metastatic behaviors, while one study even refutes its involvement in TfR1 mRNA degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": " Finally, its role as a metastasis suppressor in esophageal squamous cell carcinoma has also been described"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": ", and emerging evidence hints at interplay between innate immune receptors and miRNA pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its tumor‐regulatory functions, miR‐7 modulates cellular metabolism and cytoprotection. In pancreatic cancer, for instance, miR‐7 impairs autophagy‐derived glucose pools by activating LKB1–AMPK–mTOR signaling, thereby reducing glycolysis and restraining proliferation and metastatic spread."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": " In small cell lung cancer, diminished miR‐7 correlates with chemoresistance through derepression of the multidrug transporter MRP1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "34"}]}, {"type": "t", "text": ", while in gliomas its targeting of IGF1R alters Akt activity and impacts metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": " Moreover, in models of Parkinson disease, miR‐7 enhances glycolysis via down‐regulation of RelA and up‐regulation of the neuronal glucose transporter Glut3, thereby affording protection against mitochondrial toxin‐induced cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "36"}]}, {"type": "t", "text": " Consistently, reduced miR‐7 levels have been linked with altered autophagy and glycolytic metabolism in pancreatic cancer, underscoring its role in metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "37"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in development, cancer, and metabolism, miR‐7 orchestrates diverse signaling networks in response to hormonal, inflammatory, and environmental cues. In human osteoblasts, for example, miR‐7 targets EGFR to mediate dexamethasone‐induced cytotoxicity, with its inhibition protecting bone cells via restored EGFR–Akt signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "38"}]}, {"type": "t", "text": " Age‐related overactivation of the JAK/STAT1 pathway leads to transcriptional upregulation of miR‐7, which in turn impairs fibroblast functionality and wound healing; these deficits can be reversed by estradiol."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "39"}]}, {"type": "t", "text": " In mammary epithelial cells, hepatocyte growth factor induces miR‐7 expression, resulting in the suppression of several oncogenic targets such as EGFR and KLF4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "40"}]}, {"type": "t", "text": " Furthermore, miR‐7 modulates ion channel expression in alveolar epithelial cells, contributing to the regulation of sodium transport in acute respiratory distress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "41"}]}, {"type": "t", "text": " Finally, a rare non‐coding mutation within a primate‐specific Alu element at the MIR7‐2 locus has been implicated in dominantly inherited thyrotropin resistance through the overexpression of miR‐7 and its partner miR‐1179, causing imbalances in intracellular signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "42"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mayrin Correa-Medina, Valia Bravo-Egana, Samuel Rosero, et al. 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