{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐3619–5p is emerging as a critical tumor‐suppressive microRNA across multiple human cancers. Several studies have demonstrated that its expression is reduced in malignancies such as breast, prostate, hepatocellular, and stomach cancers, where it normally functions to inhibit oncogenic processes. For example, in breast cancer cells with lower aggressiveness, high endogenous miR‐3619 levels decrease the translation of key enzymes like PLD2, thereby contributing to a less invasive phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in prostate cancer, overexpression of miR‐3619–5p directly induces CDKN1A expression and downregulates downstream cell cycle proteins, leading to marked inhibition of cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In hepatocellular carcinoma, bioinformatic and experimental data revealed that circZFR exerts its carcinogenic effect by sponging miR‐3619–5p, ultimately resulting in upregulation of CTNNB1 and activation of the Wnt/β‐catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, miR‐3619–5p targets a spectrum of oncogenes and tumor progression mediators. In retinoblastoma, for instance, miR‐3619–5p directly binds to regulatory sites in the promoters of genes such as RIN1, and its sequestration by lncRNAs like LINC00202 facilitates tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In cutaneous squamous cell carcinoma, reduced levels of miR‐3619–5p, partly due to altered regulation by endogenous factors, lead to increased expression of KPNA4, which contributes to both enhanced proliferation and cisplatin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these direct tumor‐suppressive roles, miR‐3619–5p participates in regulating additional cellular processes. In non–small cell lung cancer, for example, it is sponged by HOXA11-AS, and its restoration results in reduced SALL4 expression, decreased proliferation, and diminished glycolytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In airway smooth muscle cells relevant to pediatric asthma, inhibition of miR‐3619–5p by LINC00882 leads to enhanced β–catenin signaling and cell proliferation in response to PDGF stimulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in stomach and liver cancers, upregulation of miR‐3619–5p has been associated with reduced cell growth, underscoring its function as a broad-spectrum inhibitor of oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In colorectal cancer, miR‐3619–5p is repressed by lncRNA LINC00958, leading to increased invasion and proliferation, while in the regulation of osteogenic differentiation, miR‐3619–5p targets BMP2 and is itself regulated by LINC01535."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In another retinoblastoma study, the lncRNA HCP5 was shown to sponge miR‐3619–5p, causing elevated HDAC9 levels and enhanced tumor cell aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, in cutaneous squamous cell carcinoma angiogenesis, miR‐3619–5p negatively regulates ROCK2 expression; its downregulation due to sequestration by circ_TNFRSF21 promotes tube formation induced by M2 macrophages."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristen Fite, Julian Gomez-Cambronero "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of MicroRNAs (MiRs) 203, 887, 3619 and 182 Prevents Vimentin-triggered, Phospholipase D (PLD)-mediated Cancer Cell Invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.686006"}], "href": "https://doi.org/10.1074/jbc.M115.686006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26567912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26567912"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Senmao Li, Chenghe Wang, Xiao Yu, et al. 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