{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn hepatocellular carcinoma, WFDC21P acts as a tumor suppressor that is directly induced by the orphan nuclear receptor Nur77. Nur77 binds to response elements on the WFDC21P promoter to activate its transcription, and the resulting WFDC21P protein inhibits tumor growth and metastasis by interfering with glycolytic remodeling. Specifically, WFDC21P interacts with two key glycolytic enzymes—PFKP and PKM2—disrupting the formation of the active PFKP tetramer and preventing PKM2’s nuclear translocation, thereby suppressing glycolysis and its oncogenic consequences. This mechanism also underlies the therapeutic effects observed with Cytosporone-B, a Nur77 agonist, which works in a WFDC21P‐dependent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, within lung carcinoma, WFDC21P appears to function as an oncogene. Here, enhanced expression of microRNA-4293 suppresses the mRNA decapping enzyme DCP2—a negative regulator of WFDC21P—resulting in elevated levels of WFDC21P. The increased expression of WFDC21P correlates with enhanced tumor cell proliferation and metastasis, and its knockdown attenuates the tumor-promoting effects of miR-4293, underscoring its direct contribution to lung cancer pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn gastric cancer, WFDC21P is significantly upregulated and its increased expression is associated with advanced disease stages. Functionally, WFDC21P promotes cellular proliferation and metastasis by directly binding to the GTPase Ran, which in turn enhances the activity of the Akt/GSK3β/β‐catenin signaling pathway. Furthermore, the transcription factor FOXP3 binds to the promoter region of WFDC21P to positively regulate its transcription, suggesting that WFDC21P may serve as both a novel biomarker and a potential therapeutic target in gastric cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yun-Feng Guan, Qiao-Ling Huang, Yuan-Li Ai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-1158-y"}], "href": "https://doi.org/10.1038/s41388-020-1158-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31959898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31959898"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qian Zhang, Yun-Fei Yan, Qing Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04021-y"}], "href": "https://doi.org/10.1038/s41419-021-04021-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34301920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34301920"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Huaiping Cui, Zhaoyu Jiang, Shujie Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new candidate oncogenic lncRNA derived from pseudogene WFDC21P promotes tumor progression in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04200-x"}], "href": "https://doi.org/10.1038/s41419-021-04200-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34601496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34601496"}]}]}]}