{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies indicate that microRNA‐545 (miR‐545) plays a multifaceted role in non‐cancerous conditions. In neurodegenerative settings, for example, a variant (miR‐545‐3p) demonstrated early biomarker potential in Alzheimer’s disease by distinguishing patients in preclinical and symptomatic stages, with levels correlating with cerebrospinal fluid Aβ42 (6). In neuronal cells under oxidative stress, decreased levels of circular RNA PRKCI led to accumulation of miR‐545, which in turn diminished the expression of the survival‐promoting transcription factor E2F7 (11). Similarly, in kidney proximal tubular epithelial cells, hypoxia‐induced upregulation of miR‐545‐3p contributed to epithelial–mesenchymal transition via inhibition of TRAIL/TNFSF10, suggesting a role in fibrotic kidney injury (19). In neonatal pneumonia models, dysregulation of miR‐545 has been linked to lipopolysaccharide‐induced cellular injury (24), and emerging evidence also hints at its involvement in delayed fracture healing (26)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various malignant tumors, miR‐545 often exhibits a tumor‐suppressive function by directly targeting key oncogenic regulators. In lung cancer cells, for instance, miR‐545 overexpression led to cell cycle arrest and apoptosis via downregulation of cyclin D1 and CDK4 (1), while in pancreatic ductal adenocarcinoma, its low expression correlated with increased levels of RIG‐I and enhanced tumor cell proliferation (3). In colorectal cancer, miR‐545 restrained tumor cell growth by inhibiting EGFR expression (7), and in gastric cancer, exogenous miR‐545 mimics suppressed epithelial–mesenchymal transition and tumor progression by targeting EMS1 (8); similar suppressive effects were observed in hepatocellular carcinoma, where miR‐545 downregulated MT1M (9). Its tumor‐inhibitory role is further supported by studies in glioma (12), ovarian cancer as part of a BRCA1/2‐directed miRNA signature (4,17), and in colorectal models where shikonin‐induced elevation of miR‐545 suppressed GNB1 expression leading to reduced proliferation (21,22)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its own functions, miR‐545 is frequently modulated by upstream long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that act as competing endogenous RNAs. For example, in hepatitis B virus‐related hepatocellular carcinoma, upregulation of the lncRNA Ftx leads to increased levels of Ftx‐derived miR‐545 that in turn promote tumor growth (2,5). In cervical cancer, circ_0067934 sequesters miR‐545, thereby relieving suppression of its target EIF3C and enhancing malignant progression (10). Similar sponging effects have been described in non‐small cell lung cancer where circ_0007580 binds miR‐545‐3p to modulate protein kinase Cα (16), in oral squamous cell carcinoma with lncRNA CASC9 sponging miR‐545‐3p to upregulate LAMC2 (20), in another NSCLC study implicating FAM83H‐AS1 in the regulation of miR‐545‐3p/HS6ST2 signaling (23), and in pancreatic cancer where circ_0018909 promotes tumor cell proliferation by sequestering miR‐545‐3p to enhance FASN expression (25)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging investigations further implicate miR‐545 in additional pathophysiological contexts. Preliminary work in colon adenocarcinoma is beginning to uncover regulatory roles for miR‐545 through LINC00342 (13), while studies in gastric cancer have revealed potential links with oncogenic lncRNAs such as SBF2‐AS1 (14,15). Moreover, recent findings in myocardial infarction models suggest that miR‐545 may also interact with inflammatory networks, broadening its potential clinical relevance (18). Together, these studies underscore the context‐dependent functions of miR‐545 and highlight its promise as a diagnostic biomarker and therapeutic target across a wide range of diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "26"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marta Cosín-Tomás, Anna Antonell, Albert Lladó, et al. 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