{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that miR‑298 plays a critical role in modulating cellular sensitivity to therapeutic agents and in neurodegenerative processes. In metastatic breast cancer cells, reduced miR‑298 levels are linked to up‐regulation of the multidrug resistance transporter P‑glycoprotein, resulting in doxorubicin resistance that can be reversed by restoring miR‑298 expression. In parallel, in Alzheimer’s disease models miR‑298 has been shown to repress key proteins in amyloid‑β production and tau modification – reducing levels of amyloid precursor protein (APP), β‑site APP‐cleaving enzyme (BACE1), and certain tau proteoforms – although its effects may vary with cell type."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several malignancies, miR‑298 is also intricately regulated by competing endogenous RNAs that modulate its tumor‐suppressive or oncogenic functions. In hepatocellular carcinoma, the long noncoding RNA LINC01287 acts as a sponge to down‐regulate miR‑298, thereby relieving miR‑298–mediated repression of MYB and promoting tumor growth. A similar ceRNA mechanism is at work in bladder cancer, where GAS6‑AS2 sequesters miR‑298 to modulate CDK9 expression and enhance cell proliferation and metastasis, and in adrenocortical cancer, where UCA1 sponging of miR‑298 results in increased CDK6 expression, accelerating cell cycle progression. Moreover, in colorectal cancer, aberrantly high miR‑298 levels promote proliferation and metastasis by targeting phosphatase and tensin homolog (PTEN), while in endometrial cancer a circular RNA (hsa_circ_0005797) sponges miR‑298 to deregulate CTNND1 expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further implicates miR‑298 in regulating the biology of other cell types. In vascular smooth muscle, for instance, circFAT1(e2) functions as a sponge for miR‑298, thereby modulating MYB expression and contributing to the pathogenesis of atrial fibrillation. In osteosarcoma, investigations aimed at delineating the impact of miR‑298 on key cellular characteristics suggest that miR‑298 may influence tumor cell proliferation, invasion, and apoptosis, although the precise molecular targets in this context remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lili Bao, Sidhartha Hazari, Smriti Mehra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of P-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2012.02.024"}], "href": "https://doi.org/10.1016/j.ajpath.2012.02.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22521303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22521303"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nipun Chopra, Ruizhi Wang, Bryan Maloney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-298 reduces levels of human amyloid-β precursor protein (APP), β-site APP-converting enzyme 1 (BACE1) and specific tau protein moieties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41380-019-0610-2"}], "href": "https://doi.org/10.1038/s41380-019-0610-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31942037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31942037"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ruizhi Wang, Debomoy K Lahiri "}, {"type": "b", "children": [{"type": "t", "text": "Effects of microRNA-298 on APP and BACE1 translation differ according to cell type and 3'-UTR variation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-022-05164-4"}], "href": "https://doi.org/10.1038/s41598-022-05164-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35197498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35197498"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yichao Mo, Longguang He, Zeru Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC01287 regulates tumorigenesis and invasion via miR-298/MYB in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13818"}], "href": "https://doi.org/10.1111/jcmm.13818"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30133116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30133116"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xin Rui, Li Wang, Huafeng Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GAS6-AS2 promotes bladder cancer proliferation and metastasis via GAS6-AS2/miR-298/CDK9 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13986"}], "href": "https://doi.org/10.1111/jcmm.13986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30394665"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30394665"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ningning Guo, Qingfeng Sun, Dongxia Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA UCA1 promoted the growth of adrenocortical cancer cells via modulating the miR-298-CDK6 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2019.03.066"}], "href": "https://doi.org/10.1016/j.gene.2019.03.066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30935924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30935924"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zahra Arabsorkhi, Ehsan Gharib, Javad Yaghmoorian Khojini, et al. 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