{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR-4653-3p plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Its expression is undetectable in the normal pancreatic duct but steadily increases from low-grade to high-grade pancreatic intraepithelial neoplasia (PanIN) and finally to PDAC, demonstrating a clear association with the neoplastic transformation and aggressiveness of the tumor. This progressive upregulation correlates with advanced pathological T stages, lymph node metastasis, and other markers of invasive disease, ultimately linking miR-4653-3p expression with poorer overall and disease-specific survival outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "At the molecular level, miR-4653-3p exerts its oncogenic effect at least partly by targeting Homeodomain Interacting Protein Kinase 2 (HIPK2). Experimental evidence in MIA PaCa-2 cells shows that miR-4653-3p downregulates HIPK2 expression, a regulatory protein whose diminished presence is observed in the progression from normal tissue through PanIN to full-blown PDAC. The decreased HIPK2 levels further correlate with more aggressive tumor features such as perineural invasion and venous involvement, underscoring the functional impact of miR-4653-3p on tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Collectively, these findings highlight miR-4653-3p as a key molecular player in PDAC tumorigenesis. By suppressing HIPK2, miR-4653-3p contributes to a more aggressive tumor phenotype and serves as a potential prognostic biomarker. Its precise role in the neoplastic cascade also suggests that targeting miR-4653-3p or restoring HIPK2 function could represent innovative therapeutic strategies for managing PDAC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kenichi Hirabayashi, Masaki Miyazawa, Yumi Takanashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4653-3p overexpression is associated with a poor prognosis of pancreatic ductal adenocarcinoma via HIPK2 downregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-022-22950-2"}], "href": "https://doi.org/10.1038/s41598-022-22950-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36289359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36289359"}]}]}]}