{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn models of Helicobacter pylori–associated gastric cancer, the bacterial virulence factor CagA downregulates miR‑4496 (in concert with miR‑320a), thereby relieving its repression of targets such as β‑catenin and ABCG2. This relief drives cancer-initiating cell (CIC) properties and chemoresistance, while restoration of miR‑4496 activity counteracts self‑renewal, tumor initiation, and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn glioma, silencing of CKAP2L results in increased miR‑4496 levels, which in turn mimic the growth‑inhibitory effects of CKAP2L knockdown. Upregulation of miR‑4496 contributes to cell cycle arrest at the G2/M checkpoint and suppresses cell proliferation, migration, invasion, and epithelial–mesenchymal transition, establishing a tumor‑suppressive role for this microRNA in neural malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn prostate cancer, the androgen receptor (AR) directly binds to miR‑4496’s promoter, enhancing its transcription. Elevated miR‑4496 then targets the 3′‑untranslated region of β‑catenin mRNA, reducing its expression and consequently suppressing cell invasion. This AR/miR‑4496/β‑catenin axis represents a novel mechanism by which AR limits metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, a separate investigation into amyotrophic lateral sclerosis focused on the roles of C21ORF2 and its interactors did not identify a functional involvement of miR‑4496, emphasizing the context‑dependent actions of this microRNA across different disease processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dong Woo Kang, Eun Sun Yang, Yu Na Noh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-320a and microRNA-4496 attenuate Helicobacter pylori cytotoxin-associated gene A (CagA)-induced cancer-initiating potential and chemoresistance by targeting β-catenin and ATP-binding cassette, subfamily G, member 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.4866"}], "href": "https://doi.org/10.1002/path.4866"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28008607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28008607"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yao-Feng Li, Wen-Chiuan Tsai, Chung-Hsing Chou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CKAP2L Knockdown Exerts Antitumor Effects by Increasing miR-4496 in Glioblastoma Cell Lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22010197"}], "href": "https://doi.org/10.3390/ijms22010197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33375517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33375517"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rui-Feng Wang, Zhi-Feng Wang, Qing Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Androgen receptor suppresses prostate cancer cell invasion via altering the miR-4496/β-catenin signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.08.134"}], "href": "https://doi.org/10.1016/j.bbrc.2018.08.134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30177389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30177389"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pavol Zelina, Anna Aster de Ruiter, Christy Kolsteeg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-024-01852-6"}], "href": "https://doi.org/10.1186/s40478-024-01852-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39227882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39227882"}]}]}]}