{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‑302b is highly expressed in stem cell populations and plays a pivotal role in regulating cell cycle, pluripotency, and differentiation. In embryonal carcinoma and embryonic stem cells, miR‑302b indirectly modulates the pluripotency marker Oct4 and directly downregulates Cyclin D2, thereby promoting self‑renewal while inhibiting neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In neuronal cells exposed to chronic ethanol, miR‑302b is robustly up‑regulated along with miR‑497 and contributes to apoptosis through a non‑mitochondrial pathway by targeting CCND2 (Cyclin D2) without inducing oxidative stress, in contrast to miR‑497 (21878650). In human embryonic stem cells, members of the miR‑302 family—including miR‑302b—directly regulate p21 expression, thereby modulating the G1/S checkpoint and the DNA damage response (22511267). Moreover, extracellular vesicles derived from non‑senescent mesenchymal stem cells increase miR‑302b levels, which in turn upregulates HIF‑1α to delay premature senescence and preserve stemness (32630449). Finally, during somatic cell reprogramming, miR‑302b participates in mRNA clearance processes that are critical for the phenotypic transition toward pluripotency (30273347)."}, {"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 oncological settings, miR‑302b generally functions as a tumor suppressor by targeting key regulators of cell proliferation, survival, and metastasis. In ovarian carcinoma cells, for example, increased miR‑302b levels enhance cisplatin sensitivity through suppression of HDAC4 (23484053), while in esophageal squamous cell carcinoma it downregulates ErbB4 expression at the post‑transcriptional level (24438167). In breast cancer, miR‑302b directly targets E2F1, leading to reduced transcriptional activation of ATM and consequent impairment of cell cycle progression and DNA repair, thereby sensitizing cells to cisplatin (26623722). In gastric cancer, reduced expression of miR‑302b is associated with increased CDK2 expression and ERK pathway activation, whereas its restoration suppresses tumor cell proliferation; similarly, sponging of miR‑302b by circular RNA circ_HN1 results in ROCK2 upregulation and oncogenic progression (27465546, 32949310). In glioblastoma, forced miR‑302b expression leads to apoptosis via direct targeting of NFIA and subsequent downregulation of IGFBP2 (28323865). Furthermore, in esophageal cancer, miR‑302b attenuates inflammation by regulating ERBB4, IRF2, and CXCR4 (28467773), and in osteosarcoma, miR‑302b downregulation is linked to enhanced migratory and invasive capabilities through derepression of Runx2 (29042587), with additional evidence implicating interactions with lncRNA FAM230B in osteosarcoma progression (35639175). Investigations in hepatocellular carcinoma have also focused on miR‑302b‐5p, while in colorectal cancer, SOX‑17 directly binds to the miR‑302b promoter to modulate invasion and apoptosis (31103408, 33739578). In laryngeal squamous cell carcinoma, miR‑302b‑3p is sequestered by lncRNA SBF2‑AS1, leading to dysregulation of TGFBR2 and enhanced metastasis (34644425), and in oral squamous cell carcinoma, overexpression of miR‑302b suppresses cell invasion by targeting FZD6 (33478325). Finally, in hepatocellular carcinoma, lncRNA UBE2R2‑AS1 acts as a competing endogenous RNA to sequester miR‑302b, thereby upregulating EGFR and promoting tumor progression (32835579)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in stemness and tumor suppression, miR‑302b is also implicated in regulating innate antiviral responses and neuroprotection. In the context of viral infection, miR‑302b (together with miR‑372) modulates mitochondrial dynamics and metabolism by attenuating the expression of SLC25A12, thereby contributing to the termination of type I interferon and cytokine production (31767682). In parallel, in models of Parkinson’s disease, IGF‑1 upregulates miR‑302b‑5p, which directly targets iNOS, leading to activation of the AKT signaling pathway and consequent neuroprotection against isoflurane‑induced neuronal injury and spatial memory impairment (32474958)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nan Sook Lee, Jong Soo Kim, Wha Ja Cho, et al. 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