{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long noncoding RNA LINC00441 plays a critical oncogenic role in several cancer types by modulating tumor suppressor pathways through distinct molecular mechanisms. In hepatocellular carcinoma (HCC), LINC00441 is aberrantly upregulated and predominantly localized in the nucleus, where its increased expression is inversely correlated with that of the neighboring tumor suppressor gene RB1. Functionally, LINC00441 promotes cell proliferation by recruiting DNA methyltransferases—specifically DNMT3A—to the RB1 promoter, leading to hypermethylation and consequent transcriptional silencing of RB1. Transcription factors such as TCF-4 further potentiate LINC00441 expression by enhancing H3K27 acetylation, thereby reinforcing its oncogenic impact."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In gastric cancer, similar epigenetic suppression of RB1 is mediated by LINC00441 through the recruitment of DNMT1, which also results in enhanced tumor cell proliferation and tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, in cervical cancer, LINC00441 exerts its oncogenic function via a distinct mechanism. It acts as a competing endogenous RNA (ceRNA) by sponging miR-450b-5p, leading to the derepression and upregulation of the RAB10 gene—a process that ultimately drives increased cellular proliferation and motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore that LINC00441 contributes to cancer progression by epigenetically silencing the tumor suppressor RB1 and by disrupting microRNA-mediated regulatory networks. Its multifunctional regulatory roles make LINC00441 a promising target for therapeutic intervention in multiple malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junwei Tang, Yu Xie, Xiaoliang Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bidirectional transcription of Linc00441 and RB1 via H3K27 modification-dependent way promotes hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2017.81"}], "href": "https://doi.org/10.1038/cddis.2017.81"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28300839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28300839"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jianping Zhou, Jun Shi, Xingli Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Linc00441 interacts with DNMT1 to regulate RB1 gene methylation and expression in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.23928"}], "href": "https://doi.org/10.18632/oncotarget.23928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30680063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30680063"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Haiyan Han, Qingchun Shao, Xuejie Liu "}, {"type": "b", "children": [{"type": "t", "text": "LINC00441 promotes cervical cancer progression by modulating miR-450b-5p/RAB10 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12935-020-01400-x"}], "href": "https://doi.org/10.1186/s12935-020-01400-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32774162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32774162"}]}]}]}