{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐28 (miR‐28), expressed as two mature products (miR‐28‑5p and miR‐28‑3p), is emerging as an important regulator in cancer, acting in a context‐dependent manner to either suppress or promote tumorigenesis. In several studies, miR‐28‑5p has been shown to directly target key oncogenic transcripts such as the antioxidant transcription factor Nrf2 in breast epithelial cells, the thrombopoietin receptor MPL in myeloproliferative neoplasms, MAD2L1 and BAG1 in Burkitt lymphoma, RAP1B in renal cell carcinoma, IGF1 in hepatocellular carcinoma, PTEN in non–small‐cell lung cancer, and MTSS1 in esophageal cancer. In addition, aberrant expression of miR‐28 (including both the 5p and 3p arms) has been associated with metastasis, recurrence, and poor clinical outcome in colorectal cancer, osteosarcoma, cholangiocarcinoma, and other malignancies. Moreover, competing endogenous RNAs (for example, CCAT1 and MCM3AP‑AS1) have been reported to sponge miR‑28‑5p in cancers such as castration‐resistant prostate cancer and breast cancer, thus impeding its tumor‐suppressive effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in modulating cancer cell proliferation, migration, invasion, and apoptosis, miR‐28 also participates in diverse regulatory circuits in non–tumor‐cell contexts. In vascular and hematologic settings, dysregulation of miR‑28 has been implicated in aberrant glycolytic metabolism—for instance, by targeting the glycolytic enzyme triose‐phosphate isomerase—and in the modulation of signaling pathways involved in endothelial senescence, parathyroid hormone regulation, and diagnostic biomarker identification in conditions like pulmonary embolism and hereditary hemorrhagic telangiectasia. Moreover, competing endogenous RNA networks (such as those involving CRNDE in chronic lymphocytic leukemia) and epigenetic alterations (including promoter methylation impacting miR‑28 expression in multiple myeloma) further underline the complexity by which miR‑28 influences diverse cellular and biochemical processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in disease, miR‐28 is involved in normal physiological processes such as cellular differentiation, tissue regeneration, and aging. Elevated miR‐28 expression has been observed during the osteogenic differentiation of mesenchymal stem cells—where it promotes differentiation by targeting negative regulators like STAT1—and in liver regeneration, where long noncoding RNAs (for example, LINC00265) modulate hepatocyte proliferation through miR‑28 sequestration. Altered circulating miR‑28‑5p levels have also been identified as potential biomarkers of premature aging, as observed in conditions such as Down syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Xu, Jian-Yong Li, Lei Fan, et al. 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