{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have highlighted an important regulatory role for miR-518a-5p in modulating oncogenic and inflammatory processes. In colorectal cancer, miR-518a-5p has been shown to directly interact with the chemokine receptor CCR6, thereby modulating its expression and influencing tumor cell behavior. The data indicate that miR-518a-5p acts to attenuate CCR6 expression, which may contribute to reduced chemotactic and proliferative signals in colorectal cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn imatinib-resistant gastrointestinal stromal tumors, downregulation of miR-518a-5p has been correlated with increased expression of the target gene PIK3C2A. Functional experiments demonstrated that enforced expression of miR-518a-5p suppresses PIK3C2A, leading to decreased cell proliferation and enhanced apoptosis in resistant tumor cells. This finding suggests that miR-518a-5p may act as a tumor suppressor, and its reduced expression could be one mechanism underlying drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of inflammatory diseases such as rheumatoid arthritis, miR-518a-5p is negatively regulated by the proinflammatory cytokine CCN1 via the MAPK signaling cascade. CCN1-induced downregulation of miR-518a-5p correlates with an upregulation of the monocyte chemoattractant protein CCL2 in osteoblasts, thereby promoting monocyte migration and contributing to the pathogenesis of rheumatoid arthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, in diffuse large B cell lymphoma, miR-518a-5p has been found to inversely correlate with CCR6 expression. Overexpression of miR-518a-5p leads to reduced CCR6 levels and subsequent downregulation of downstream signaling pathways such as JAK2/STAT6, which in turn diminishes cell proliferation and invasion. Epigenetic modifications affecting the promoter region of miR-518a-5p have also been reported, suggesting an additional layer of regulation in lymphomagenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Claudia Rubie, Bianca Kruse, Vilma Oliveira Frick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1479-5876-12-48"}], "href": "https://doi.org/10.1186/1479-5876-12-48"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24559209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24559209"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuan Shi, Xiaodong Gao, Qin Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PIK3C2A is a gene-specific target of microRNA-518a-5p in imatinib mesylate-resistant gastrointestinal stromal tumor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/labinvest.2015.157"}], "href": "https://doi.org/10.1038/labinvest.2015.157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26950487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26950487"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cheng-Yu Chen, Lih-Jyh Fuh, Chien-Chung Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-00513-0"}], "href": "https://doi.org/10.1038/s41598-017-00513-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28341837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28341837"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qian Huang, Feng Zhang, Haiying Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic regulation of miR-518a-5p-CCR6 feedback loop promotes both proliferation and invasion in diffuse large B cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15592294.2020.1786317"}], "href": "https://doi.org/10.1080/15592294.2020.1786317"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32600091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32600091"}]}]}]}