{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn glioblastoma multiforme, overexpression of miR‑4698 in concert with miR‑548x was shown to suppress tumor cell proliferation by targeting critical components of the PI3K/AKT pathway – including PDK1, RHEB, and mTOR – leading to cell cycle arrest and downregulation of AKT1 protein expression. These findings support a tumor‐suppressive role for miR‑4698 in glioblastoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn hepatocellular carcinoma, miR‑4698 expression is markedly lower in tumor tissues compared to normal counterparts. Experimental overexpression of miR‑4698 in HCC cells resulted in significant inhibition of proliferation, migration, invasion, and epithelial–mesenchymal transition. Mechanistically, miR‑4698 targets the oncogenic protein Trim59, and restoration of miR‑4698 levels effectively suppresses the malignant phenotype, underscoring its tumor‐suppressive function in HCC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, in gastric carcinoma, miR‑4698 is found to be upregulated in tumor tissues where it exerts an oncogenic influence by directly targeting MTUS1, a gene with tumor‐suppressive properties. The long non‑coding RNA LIFR‑AS1, which is downregulated in these cancers, can sequester miR‑4698; this interaction leads to restoration of MTUS1 expression and subsequent inhibition of the MEK/ERK signaling pathway, thereby restraining cancer cell proliferation, migration, and invasion. These observations highlight a context‑dependent role for miR‑4698 in gastric carcinoma, where its overactivity contributes to oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mohammad Reza Kalhori, Ehsan Arefian, Fereshteh Fallah Atanaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-548x and miR-4698 controlled cell proliferation by affecting the PI3K/AKT signaling pathway in Glioblastoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-57588-5"}], "href": "https://doi.org/10.1038/s41598-020-57588-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32005873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32005873"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dandan Yu, Liqing Zhu, Hongxiang Tu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4698-Trim59 axis plays a suppressive role in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Biosci (Landmark Ed) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2741/4849"}], "href": "https://doi.org/10.2741/4849"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32114426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32114426"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jiangqiao Zhao, Xiaoning Li, Liping Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA LIFR‑AS1 inhibits gastric carcinoma cell proliferation, migration and invasion by sponging miR‑4698."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2020.11792"}], "href": "https://doi.org/10.3892/mmr.2020.11792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33355363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33355363"}]}]}]}