{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have highlighted microRNA‐4500 as a critical tumor suppressor whose reduced expression is associated with advanced tumor stage, poor clinical outcomes, and aggressive tumor behavior. In colorectal cancer, for example, miR‐4500 expression is diminished—largely due to hypermethylation of its promoter—and its loss facilitates enhanced cell proliferation, cell cycle progression, migration, and invasion by failing to curb oncogenic targets such as HMGA2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to colorectal cancer, miR‐4500 exerts tumor‐suppressive functions in several other malignancies. In glioma, the microRNA directly targets IGF2BP1, which in turn downregulates crucial downstream effectors including Gli1, IGF2, and c‐Myc, leading to inhibited tumor cell growth, survival, and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In papillary thyroid cancer, miR‐4500 overexpression impedes cancer progression by targeting PLXNC1, thereby reducing colony formation, proliferation, and invasion while promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in non‐small cell lung cancer, miR‐4500 downregulates STAT3 expression with subsequent reduction in cell proliferation and migration alongside enhanced apoptotic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In ovarian cancer, miR‐4500 is functionally sequestered by the long noncoding RNA NEAT1, resulting in the upregulation of BZW1; this axis contributes to increased proliferation, invasion, and glycolysis, emphasizing miR‐4500’s role in mitigating oncogenic signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings underscore the multifaceted tumor‐suppressive role of miR‐4500 across diverse cancer types, suggesting that restoring its function may be a promising therapeutic approach. Although current research has largely focused on its impact in malignancies, emerging studies on endothelial senescence—an underlying contributor to cardiovascular diseases—hint at potential avenues for exploring miR‐4500’s regulatory networks in non‐cancer contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Feng Yan Yu, Yun Tu, Ying Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384047.2016.1235661"}], "href": "https://doi.org/10.1080/15384047.2016.1235661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27686621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27686621"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zheng-Wei Li, Min Xue, Bing-Xin Zhu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MiR-4500 Regulates PLXNC1 and Inhibits Papillary Thyroid Cancer Progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Horm Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12672-019-00366-1"}], "href": "https://doi.org/10.1007/s12672-019-00366-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31317324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31317324"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhi-Ying Li, Zi-Zhou Zhang, Hui Bi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA‑4500 suppresses tumor progression in non‑small cell lung cancer by regulating STAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2019.10737"}], "href": "https://doi.org/10.3892/mmr.2019.10737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31638206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31638206"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hongying Xu, Xiaowei Sun, Ying Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non‑coding RNA NEAT1 modifies cell proliferation, colony formation, apoptosis, migration and invasion via the miR‑4500/BZW1 axis in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2020.11408"}], "href": "https://doi.org/10.3892/mmr.2020.11408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32945505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32945505"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yajun Wang, Yang Li, Yirong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The lncRNA OIP5-AS1/miR-4500 axis targeting ARG2 modulates oxidative stress-induced premature senescence in endothelial cells: implications for vascular aging."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Expert Opin Ther Targets (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/14728222.2023.2216382"}], "href": "https://doi.org/10.1080/14728222.2023.2216382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37203350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37203350"}]}]}]}