{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRTKN2 has emerged as an important mediator in several solid tumors where its dysregulation contributes to oncogenic processes. In hepatocellular carcinoma, for example, RTKN2 is upregulated through a ceRNA mechanism involving hsa_circRNA_104348 and miR‐187‐3p, thereby promoting proliferation, migration, invasion, and attenuating apoptosis via pathways such as Wnt/β‐catenin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similar oncogenic roles have been observed in other cancers; in HCC, RTKN2 overexpression drives cell cycle progression and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in colorectal cancer, circZFR-mediated sponging of miR-3127-5p results in elevated RTKN2 levels that favor tumor growth and spread."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In ovarian cancer, decreased miR-181 leads to insufficient suppression of RTKN2, which in turn contributes to tumorigenesis via NF-κB signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Additionally, studies in lung adenocarcinoma and breast cancer demonstrate that elevated RTKN2 expression is associated with enhanced tumor cell proliferation, migration, and invasion, in part by modulating the Wnt/β-catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in malignant transformation, RTKN2 is also functionally significant in the immune system. Initial characterizations revealed that RTKN2 is predominantly expressed in CD4-positive T-cells and bone marrow–derived B-cells, with expression increasing in quiescent T-cells. This pattern suggests a potential role in lymphopoiesis and immune regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, genetic studies in rheumatoid arthritis have identified risk alleles in the RTKN2 locus that may enhance NF-κB activity and contribute to the disease’s inflammatory pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRTKN2 also exerts an anti-apoptotic influence in non-cancer contexts. In human keratinocytes, miR-1246 directly targets RTKN2, and its UVB-induced upregulation promotes apoptosis by relieving RTKN2-dependent resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, a loss-of-function mutation in RTKN2 was identified in a dilated cardiomyopathy cohort, implicating aberrant RTKN2 function in cardiac pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guanqun Huang, Min Liang, Haiyan Liu, et al. 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