{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐765 is emerging as a context‐dependent regulator in a wide variety of human diseases. In estrogen‐dependent uterine corpus endometrial cancer, miR‐765 is markedly downregulated by ERβ signaling, which in turn unleashes a cluster‐mediated upregulation of targets such as PLP2 that drive epithelial–mesenchymal transition and cell proliferation. Conversely, in hepatocellular carcinoma, miR‐765 is overexpressed and functions as an onco–miRNA by directly repressing INPP4B, thereby inducing AKT activation and cell‐cycle progression. In soft tissue sarcomas, although miR‐765 is observed to be overexpressed, its silencing activity on the tumor suppressor SMARCB1 is functionally negligible. Moreover, elevated circulating levels of miR‐765 have been reported in geriatric coronary artery disease, highlighting its potential as a noninvasive diagnostic biomarker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several other malignancies, miR‐765 exerts pivotal functions by targeting key oncogenic or tumor–suppressive pathways. In melanoma, for instance, endoplasmic reticulum stress induces HOXB9, which transcriptionally activates miR‐765; this microRNA then decreases FOXA2 levels, leading to an expansion of cancer stem cells and enhanced tumorigenesis. In pancreatic cancer, the long non–coding RNA LINC00994 sequesters miR‐765, thereby relieving its repression on RUNX2 and promoting aggressive cell behavior. In primary breast carcinoma, reduced miR‐765 is associated with overexpression of EMP3, correlating with increased proliferation and invasion. Ovarian cancer cells, on the other hand, become more vulnerable to apoptosis and less migratory when miR‐765 suppresses BRD4 expression, while in gastric cancer, elevated miR‐765 has been linked to multidrug resistance through inhibition of a tumor suppressor transcription factor. Early work in osteosarcoma has also suggested that aberrant miR‐765 expression may contribute to tumorigenicity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, miR‐765 is also involved in diverse non–oncological processes. In the vascular system, a single nucleotide polymorphism within an miR‐765 binding site in the 3′–UTR of apelin (APLN) alters gene expression and influences arterial stiffness. In the setting of atherosclerosis, a specific circular RNA functions as a sponge for miR‐765 in ox–LDL–stimulated macrophages; this derepression of EFNA3 culminates in activation of the NLRP3 inflammasome and an enhanced inflammatory response. In type 2 diabetes mellitus, miR‐765 overexpression in pancreatic β–cells results in downregulation of PDX1, thereby impairing insulin secretion, cell viability, and mitochondrial respiration. Additionally, preliminary evidence suggests a regulatory role for miR‐765 in the osteogenic differentiation of human bone marrow mesenchymal stem cells, with potential implications for tissue repair. A recent review further underscores how miR‐765 modulates multiple pathways—including those associated with PLP2/Notch, VEGFA/Akt1, and RUNX2—and highlights its promise as an early biomarker for tumor progression and as a novel therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Md Sayed Ali Sheikh, Ke Xia, Fei Li, et al. 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