{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn esophageal carcinoma, miR‑4286 is highly expressed and has been shown to promote cell viability, migration, and invasion by directly targeting INPP4A and activating the JAK2/STAT3 pathway, thereby contributing to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In non–small cell lung cancer, two independent studies have further implicated miR‑4286 in oncogenesis: one study demonstrated that miR‑4286 binds to the 3′‑untranslated region of PTEN, leading to reduced expression of this key tumor suppressor and enhanced tumor proliferation and mobility"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and another revealed that miR‑4286 upregulation promotes cell cycle progression while inhibiting apoptosis through modulation of the transcription factor Runx3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlthough the role of miR‑4286 in prostate cancer remains unexplored"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", studies in other tumor types have uncovered contrasting roles. In glioblastoma, IGF‑1 stimulation decreases miR‑4286 expression, which in turn facilitates mesenchymal transition and cell invasion via upregulation of TGF‑β pathway effectors, TGFB1 and TGFBR2—a process that can be reversed by restoring miR‑4286 levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In contrast, in Helicobacter pylori–associated gastric cancer, elevated serum miR‑4286 correlates positively with tumor stage, tumor size, and lymph node metastasis, and its overexpression drives cancer cell proliferation and motility by targeting BZRAP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumor biology, circulating miR‑4286 has emerged as a potential biomarker in cardiovascular disease: higher plasma levels are associated with an increased risk of acute coronary syndrome, possibly by mediating the proatherogenic effects of elevated triglycerides."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, preliminary evidence suggests that miR‑4286 may play a protective role in alcohol-induced bone loss, further underscoring its context‑dependent functions across diverse tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Meng Zhang, Hui Tian, Rongrong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-4286 promotes esophageal carcinoma development by targeting INPP4A to evoke the JAK2/STAT3 pathway activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmazie (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1691/ph.2018.7339"}], "href": "https://doi.org/10.1691/ph.2018.7339"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29880087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29880087"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chunhua Ling, Xueting Wang, Jianjie Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-4286 promotes cell proliferation, migration, and invasion via PTEN regulation of the PI3K/Akt pathway in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2220"}], "href": "https://doi.org/10.1002/cam4.2220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31074594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31074594"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xian An, Jiwen Ge, Huihui Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of miR-4286 is an unfavorable prognostic marker in individuals with non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29024"}], "href": "https://doi.org/10.1002/jcb.29024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31111550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31111550"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhanqi Li, Shaoxiong Zhao, Hui Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4286 promotes prostate cancer progression by targeting the expression of SALL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gene Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jgm.3127"}], "href": "https://doi.org/10.1002/jgm.3127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31693770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31693770"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kuo-Hao Ho, Peng-Hsu Chen, Chwen-Ming Shih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4286 is Involved in Connections Between IGF-1 and TGF-β Signaling for the Mesenchymal Transition and Invasion by Glioblastomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Neurobiol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10571-020-00977-1"}], "href": "https://doi.org/10.1007/s10571-020-00977-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33025417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33025417"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chin-Chuan Tsai, Tai-Yu Chen, Kuen-Jang Tsai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-Associated gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2020.110869"}], "href": "https://doi.org/10.1016/j.biopha.2020.110869"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33113427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33113427"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Miaoyan Shen, Xuedan Xu, Xuezhen Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prospective Study on Plasma MicroRNA-4286 and Incident Acute Coronary Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Heart Assoc (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/JAHA.120.018999"}], "href": "https://doi.org/10.1161/JAHA.120.018999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33719498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33719498"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hongping Yu, Kaiyang Wang, Pei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4286 functions in osteogenesis and angiogenesis via targeting histone deacetylase 3 and alleviates alcohol-induced bone loss in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Prolif (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cpr.13054"}], "href": "https://doi.org/10.1111/cpr.13054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33973278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33973278"}]}]}]}