{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified miR-5590-3p as a key regulator of tumor suppressive pathways. In one investigation, overexpression of hsa‐miR‐5590-3p was shown to negatively regulate the transforming growth factor‑β (TGFβ)/SMAD signaling cascade by directly targeting the 3′UTRs of TGFβ receptors (TGFβ-R1 and TGFβ-R2) as well as SMAD3 and SMAD4. This downregulation was accompanied by decreased receptor protein levels and induction of cell cycle arrest, with notably lower miR-5590-3p levels observed in advanced breast tumor samples, suggesting its potential utility as a therapeutic target in cancers where TGFβ/SMAD signaling is deregulated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nIn hepatocellular carcinoma (HCC), another study demonstrated that the long non-coding RNA SOX9-AS1 acts as a competing endogenous RNA by sponging miR-5590-3p. This interaction alleviates the miRNA-mediated repression of the oncogene SOX9, leading to its overexpression and subsequent activation of the Wnt/β-catenin pathway, which in turn facilitates tumor growth, epithelial-to-mesenchymal transition, and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \nA further layer of complexity is observed in renal cell carcinoma (RCC), where miR-5590-3p has been alternatively referred to as lncRNA FGD5-AS1. In this context, it is implicated in the intricate competing endogenous RNA networks that regulate clear cell proliferation and metastatic progression, although its precise molecular functions in RCC require further elucidation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n \nIn ovarian cancer, miR-5590-3p also emerges as a potent tumor suppressor. Its downregulation in cancer cells leads to the derepression of TNIK, a target gene that activates the Wnt/β-catenin signaling pathway, thereby promoting cell proliferation and invasion. Conversely, restoration of miR-5590-3p levels inhibits TNIK expression, suppresses the malignant phenotype, and reduces tumor growth in vivo, highlighting its promise as a therapeutic candidate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elham Abedini Bakhshmand, Bahram Mohammad Soltani "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2018-0264"}], "href": "https://doi.org/10.1515/hsz-2018-0264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30391930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30391930"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wei Zhang, Yanhui Wu, Bingwu Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/β-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12560"}], "href": "https://doi.org/10.1002/1878-0261.12560"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31402556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31402556"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Y Yang, M-H Dong, H-M Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FGD5-AS1/miR-5590-3p axis facilitates the proliferation and metastasis of renal cell carcinoma through ERK/AKT signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202009_22814"}], "href": "https://doi.org/10.26355/eurrev_202009_22814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32964964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32964964"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaoling Wu, Youwen Zhong, Hua Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-5590-3p inhibits the proliferation and invasion of ovarian cancer cells through mediating the Wnt/β-catenin signaling pathway by targeting TNIK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-18-636"}], "href": "https://doi.org/10.14670/HH-18-636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37318197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37318197"}]}]}]}