{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‑125a is a versatile non‑coding RNA whose proper biogenesis is critical for its regulatory functions. Genetic variations such as a single‐nucleotide polymorphism in the miR‑125a precursor can impair processing from primary to precursor forms and consequently reduce its translational repression of target genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In breast cancer, miR‑125a represses the oncogenic RNA‑binding protein HuR, thereby inhibiting cell growth and migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in ovarian cancer, downregulation of miR‑125a by EGFR signaling contributes to epithelial‑to‑mesenchymal transition (EMT) via diminished ARID3B regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In non‑small‑cell lung cancer (NSCLC), distinct mature isoforms of miR‑125a (–3p/–5p) modulate invasive and migratory behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nmiR‑125a also regulates multiple oncogenic signaling pathways in diverse malignancies. In glioblastoma, the microRNA together with miR‑29b directly targets PDPN to impede cell proliferation and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and in gastric cancer it functions as a tumor suppressor by modulating the ERBB2 pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Its antiviral activity is highlighted by its ability to interact with hepatitis B virus genomic sequences, thereby suppressing viral antigen expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In lung cancer cells, miR‑125a‑5p has been shown to induce apoptosis in a p53‑dependent manner"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while in diffuse large B‑cell lymphoma overexpression of miR‑125a (often together with its paralog miR‑125b) targets the negative NF‑κB regulator TNFAIP3, thereby enhancing NF‑κB signaling and contributing to lymphomagenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncogenic signaling, aberrant miR‑125a expression influences the tumor microenvironment, immune balance, and diagnostic biomarker potential. Although its role in hepatocellular carcinoma remains to be fully elucidated"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", miR‑125a‑5p is a key regulator of blood–brain barrier tightness and immune cell efflux in neurological disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In NSCLC, circulating miR‑125a‑5p levels have been proposed as a promising diagnostic biomarker"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while its restoration in colon cancer cells promotes apoptosis via downregulation of anti‑apoptotic factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, reduced miR‑125a expression in cervical cancer correlates with increased STAT3 signaling and aggressive tumor behavior"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", and its downregulation in autoimmune conditions destabilizes regulatory T‑cell homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Altered miR‑125a levels have additionally been linked to endothelial dysfunction in pediatric cardiovascular risk"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "and to modulation of cancer stem cell properties in breast cancer via indirect regulation of the LIFR–TAZ axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nmiR‑125a further impacts cellular metabolism and apoptotic pathways, underscoring its multifaceted regulatory role. 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"}, {"type": "b", "children": [{"type": "t", "text": "miR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20808"}], "href": "https://doi.org/10.1002/gcc.20808"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20665731"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20665731"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Naohiro Nishida, Koshi Mimori, Muller Fabbri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-10-2132"}], "href": "https://doi.org/10.1158/1078-0432.CCR-10-2132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21220473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21220473"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nicoletta Potenza, Umberto Papa, Nicola Mosca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkr067"}], "href": "https://doi.org/10.1093/nar/gkr067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21317190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21317190"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lili Jiang, Qin Huang, Jihong Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA HSA-miR-125a-5p induces apoptosis by activating p53 in lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Lung Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/01902148.2010.492068"}], "href": "https://doi.org/10.3109/01902148.2010.492068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21777146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21777146"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sang-Woo Kim, Kumaraguruparan Ramasamy, Hakim Bouamar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs miR-125a and miR-125b constitutively activate the NF-κB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1200081109"}], "href": "https://doi.org/10.1073/pnas.1200081109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22550173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22550173"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Qian Bi, Shanhong Tang, Lin Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0040169"}], "href": "https://doi.org/10.1371/journal.pone.0040169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22768249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22768249"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Arie Reijerkerk, M Alejandro Lopez-Ramirez, Bert van Het Hof, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.3965-12.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.3965-12.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23595744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23595744"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Rui-Juan Wang, Yan-Hua Zheng, Ping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25755772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25755772"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Zhiguo Tong, Nan Liu, Luoqiang Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer via targeting BCL2, BCL2L12 and MCL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2015.07.036"}], "href": "https://doi.org/10.1016/j.biopha.2015.07.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26297542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26297542"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zhongyi Fan, Hanzhi Cui, Xiaojie Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4457"}], "href": "https://doi.org/10.18632/oncotarget.4457"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26389681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26389681"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Wen Pan, Shu Zhu, Dai Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms8096"}], "href": "https://doi.org/10.1038/ncomms8096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25963922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25963922"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Abdelnaby Khalyfa, Leila Kheirandish-Gozal, Rakesh Bhattacharjee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating microRNAs as Potential Biomarkers of Endothelial Dysfunction in Obese Children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chest (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1378/chest.15-0799"}], "href": "https://doi.org/10.1378/chest.15-0799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26270249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26270249"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sushmita Bose Nandy, Arunkumar Arumugam, Ramadevi Subramani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-125a influences breast cancer stem cells by targeting leukemia inhibitory factor receptor which regulates the Hippo signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.3953"}], "href": "https://doi.org/10.18632/oncotarget.3953"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25962054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25962054"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jianlin Ma, Yun Zhan, Zhipeng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZEB1 induced miR-99b/let-7e/miR-125a cluster promotes invasion and metastasis in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2017.04.006"}], "href": "https://doi.org/10.1016/j.canlet.2017.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28408353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28408353"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Lihi Ninio-Many, Hadas Grossman, Noam Shomron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-125a-3p reduces cell proliferation and migration by targeting Fyn."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.123414"}], "href": "https://doi.org/10.1242/jcs.123414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23606749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23606749"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Lichao Pan, Lin Zhou, Weijia Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-125a induces apoptosis, metabolism disorder and migrationimpairment in pancreatic cancer cells by targeting Mfn2-related mitochondrial fission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2018.4380"}], "href": "https://doi.org/10.3892/ijo.2018.4380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29749475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29749475"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Zeng Zhaolin, Chen Jiaojiao, Wu Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.27509"}], "href": "https://doi.org/10.1002/jcp.27509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30370524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30370524"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Jing Wang, Feihu Yan, Qi Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating exosomal miR-125a-3p as a novel biomarker for early-stage colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-04386-1"}], "href": "https://doi.org/10.1038/s41598-017-04386-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28646161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28646161"}]}]}]}