{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long noncoding RNA BACE1‐AS is emerging as a critical regulator of β‐secretase 1 (BACE1) expression through multiple post‐transcriptional mechanisms. In Alzheimer’s disease, BACE1‐AS is upregulated in response to cellular stress (such as exposure to amyloid‑β peptides), where it forms RNA duplexes with BACE1 mRNA and/or acts as a competing endogenous RNA that sequesters microRNAs targeting BACE1. Together, these processes enhance BACE1 mRNA stability and protein production, thereby fueling a feed‑forward loop that increases amyloid‑β generation and contributes to disease pathology (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " Beyond the brain, increased BACE1‑AS expression has been tied to elevated BACE1 levels and β‑amyloid accumulation in cardiac tissues, suggesting a pathologic role in heart failure, while aberrant expression in peripheral blood samples further indicates its potential utility as a blood‑based biomarker for Alzheimer’s disease (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, emerging evidence in oncological models demonstrates that BACE1‑AS may contribute to tumor progression by sponging specific microRNAs and thereby regulating downstream oncogenic targets, although its direction of regulation appears context‑dependent (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": " Finally, studies in neurodevelopmental disorders such as autism further support a correlation between BACE1‑AS and altered BACE1 expression, implicating this lncRNA as a broader regulator of neuronal function (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Together, these findings underscore BACE1‑AS as a pivotal molecular node that modulates BACE1 levels via dual mechanisms—direct stabilization through RNA duplex formation and indirect regulation via microRNA sponging—with significant implications for Alzheimer’s pathogenesis and potentially other disease processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mohammad Ali Faghihi, Farzaneh Modarresi, Ahmad M Khalil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1784"}], "href": "https://doi.org/10.1038/nm1784"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18587408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18587408"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Min-Ju Kang, Kotb Abdelmohsen, Emmette R Hutchison, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HuD regulates coding and noncoding RNA to induce APP→Aβ processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2014.04.050"}], "href": "https://doi.org/10.1016/j.celrep.2014.04.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24857657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24857657"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Te Liu, Yongyi Huang, Jiulin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2014.2351"}], "href": "https://doi.org/10.3892/mmr.2014.2351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24970022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24970022"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tao Zeng, Haitao Ni, Yue Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Chem Neuroanat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jchemneu.2019.04.001"}], "href": "https://doi.org/10.1016/j.jchemneu.2019.04.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30959172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30959172"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Seyedeh Nahid Fotuhi, Mohammad Khalaj-Kondori, Mohammad Ali Hoseinpour Feizi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long Non-coding RNA BACE1-AS May Serve as an Alzheimer's Disease Blood-Based Biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-019-01364-2"}], "href": "https://doi.org/10.1007/s12031-019-01364-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31264051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31264051"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Simona Greco, Germana Zaccagnini, Paola Fuschi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased BACE1-AS long noncoding RNA and β-amyloid levels in heart failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvx013"}], "href": "https://doi.org/10.1093/cvr/cvx013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28158647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28158647"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuan Zhou, Yao Ge, Qi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA BACE1-AS Promotes Autophagy-Mediated Neuronal Damage Through The miR-214-3p/ATG5 Signalling Axis In Alzheimer's Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2020.10.028"}], "href": "https://doi.org/10.1016/j.neuroscience.2020.10.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33197504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33197504"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mengmeng Wang, Di Chen, Yushuang Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and Validation of the lncRNA BACE1-AS as Immune-Related Influencing Factor in Tumorigenesis following Pan-Carcinoma Analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/1589864"}], "href": "https://doi.org/10.1155/2021/1589864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34926701"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34926701"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Farbod Esfandi, Soudeh Ghafouri-Fard, Vahid Kholghi Oskooei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "β-Secretase 1 and its Naturally Occurring Anti-Sense RNA are Down-Regulated in Gastric Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12253-019-00621-4"}], "href": "https://doi.org/10.1007/s12253-019-00621-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30805871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30805871"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chunlei Wang, Tao Zhang, Lin Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA BACE1-AS promotes the progression of osteosarcoma through miR-762/SOX7 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-022-07364-7"}], "href": "https://doi.org/10.1007/s11033-022-07364-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35332412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35332412"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Soudeh Ghafouri-Fard, Amir Namvar, Shahram Arsang-Jang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression Analysis of BDNF, BACE1, and Their Natural Occurring Antisenses in Autistic Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-019-01432-7"}], "href": "https://doi.org/10.1007/s12031-019-01432-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31760580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31760580"}]}]}]}