{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00476, a long non‐coding RNA, has recently been implicated in the regulation of tumor progression and chemotherapy response in several cancers. In non‐small cell lung cancer, LINC00476 is significantly downregulated in tumor tissues relative to adjacent normal tissues. Functional experiments demonstrated that its overexpression induces the ubiquitination‐mediated degradation of SETDB1, thereby inhibiting the activation of the Wnt/β‐catenin pathway. This mechanism contributes to its tumor‐suppressive role by reducing cellular proliferation, invasion, and migration, as well as by suppressing tumor growth in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pancreatic cancer, LINC00476 has been identified as one of four long non‐coding RNAs used to construct a prognostic risk score system. Its expression is associated with patient survival and is correlated with various oncogenic pathways—including those involved in Ras activation, MAPK signaling, autophagy, HIF‐1, and PI3K–Akt signaling—suggesting that LINC00476 may modulate multiple biological processes relevant to cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, in the context of metastatic colorectal cancer, LINC00476 has emerged as a component of an eight‐lncRNA signature predictive of response to FOLFOX chemotherapy. Functional enrichment analysis of this signature implicated the MAPK and proteoglycan signaling pathways in mediating chemotherapy resistance, highlighting the potential utility of LINC00476 as a biomarker for treatment response and prognosis."}, {"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 studies suggest that LINC00476 acts as a tumor suppressor in NSCLC and may serve as a prognostic and predictive biomarker in pancreatic and colorectal cancers by modulating key oncogenic signaling pathways.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guanghui Cui, Xiao Fu, Wentao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00476 Suppresses the Progression of Non-Small Cell Lung Cancer by Inducing the Ubiquitination of SETDB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Radiat Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1667/RADE-20-00105.1"}], "href": "https://doi.org/10.1667/RADE-20-00105.1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33370431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33370431"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hongkai Zhuang, Shanzhou Huang, Zixuan Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer."}]}, {"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/s12935-020-01588-y"}], "href": "https://doi.org/10.1186/s12935-020-01588-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33061845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33061845"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yiyi Zhang, Meifang Xu, Yanwu Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of LncRNAs Associated With FOLFOX Chemoresistance in mCRC and Construction of a Predictive Model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2020.609832"}], "href": "https://doi.org/10.3389/fcell.2020.609832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33585448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33585448"}]}]}]}