{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that miR‐1247, including its 3p and 5p isoforms, plays diverse and context‐dependent roles in normal physiology and cancer. In non‐malignant settings, miR‑1247 is involved in skeletal development, where in human chondrocytes its expression is tightly correlated with a differentiated phenotype and it directly regulates the master chondrogenic transcription factor SOX9 (as demonstrated in PMID 24014021."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, epigenetic silencing via DNA hypermethylation has been shown to downregulate MIR1247 in gastric cancers, thereby contributing to tumor progression (PMID 24785261."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In osteosarcoma stem cells, reduced miR‑1247 expression has been linked to enhanced metastatic abilities, potentially through dysregulation of MAP3K9 signaling (PMID 25973030."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several cancer types, miR‑1247 functions as a tumor suppressor. For instance, in pancreatic cancer, restoration of miR‑1247 expression impairs cell growth and invasion by targeting RCC2 (PMID 28460450"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma (HCC) its downregulation—specifically the miR‑1247‑5p strand—leads to unchecked Wnt3 signaling and tumor progression; conversely, re‐expression of miR‑1247‑5p suppresses proliferation and invasion in HCC cells (PMID 28586038."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Reduced miR‑1247 levels have also been correlated with aggressive features in breast cancer, where decreased expression is associated with larger tumor size, advanced stage, and poor survival, with direct targets identified such as DVL1 (PMID 30175411"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and PMID 30249392."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In bladder cancer, intracellular miR‑1247 acts to curb tumor cell proliferation and invasion by targeting RAB36 (PMID 29872024"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and its overexpression in glioma leads to downregulation of CDC14B, thereby stabilizing p53 activity and inhibiting malignancy (PMID 32366555."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, similar tumor‐suppressive roles have been observed in colon cancer (PMID 30318507"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and have been implicated in osteosarcoma and neuroblastoma models (PMID 31539113"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "and PMID 29793538"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", respectively).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, miR‑1247 also exhibits oncogenic properties when acting in intercellular communication. In the metastatic niche of HCC, highly aggressive tumor cells secrete exosomal miR‑1247‑3p that targets B4GALT3 in normal fibroblasts, thereby activating β1‐integrin–NF‑κB signaling to convert them into cancer‐associated fibroblasts (CAFs) and promote lung metastasis (PMID 29335551."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In cutaneous squamous cell carcinoma, overexpressed circRNAs such as circ_0070934 act as sponges for miR‑1247‑5p, mitigating its tumor‑suppressive effects and thereby favoring cell proliferation, migration, and invasion (PMID 30967263."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In prostate cancer, a reduction of miR‑1247—mediated by signals from cancer‐associated fibroblasts—has been implicated in promoting epithelial-to-mesenchymal transition and enhanced stemness, partly via increased neuropilin‑1 expression (PMID 30378132."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Additionally, contrasting expression patterns are noted in other malignancies; for example, miR‑1247 levels are elevated in metastatic uveal melanoma (PMID 32131485"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "and in certain adrenal tumors affecting Wnt signaling (PMID 35887024."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Finally, in bladder cancer, exosomal miR‑1247‑3p has been further shown to promote angiogenesis through the direct targeting of FOXO1, underscoring its multifaceted roles depending on its cellular context and mode of transfer (PMID 38073044."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aida Martinez-Sanchez, Chris L Murphy "}, {"type": "b", "children": [{"type": "t", "text": "miR-1247 functions by targeting cartilage transcription factor SOX9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.496729"}], "href": "https://doi.org/10.1074/jbc.M113.496729"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24014021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24014021"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joong-Gook Kim, Tae-Oh Kim, Jin-Han Bae, et al. 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