{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Multiple studies have implicated the insulin‐growth factor–like family member 2 (IGFL2) and its antisense long noncoding transcript (IGFL2‐AS1) in diverse pathological contexts. In Sézary syndrome, for example, IGFL2 is among a set of novel genes significantly overexpressed in malignant CD4+ T cells compared with controls, suggesting a potential role in disease diagnosis and pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cutaneous T‐cell lymphoma, IGFL2 has been linked to metabolic dysregulation; genetic polymorphisms in IGFL2 are associated with elevated fasting plasma glucose levels and an increased risk of type 2 diabetes mellitus, highlighting its potential metabolic significance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In proteomic analyses aimed at detecting missing proteins, IGFL2 has also been identified in human placenta, confirming its translational expression and hinting at broader biological roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n The antisense transcript IGFL2‐AS1 emerges as a critical regulatory RNA in multiple cancers. In gastric cancer, IGFL2‐AS1 is highly expressed and functions as a competitive endogenous RNA by sponging miR‐802, thereby promoting tumor cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similar oncogenic roles for IGFL2‐AS1 have been observed in basal‐like breast cancer, where it cooperates with transcription factors to upregulate its neighboring IGFL1 and support pro‐survival and proliferative pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In tongue squamous cell carcinoma, IGFL2‐AS1 enhances tumor progression by acting as a molecular sponge for miR‐1224‐5p, which in turn modulates the expression of SATB1 and activates the Wnt/β‐catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, IGFL2‐AS1 has been implicated in broader competing endogenous RNA (ceRNA) networks that influence tumor progression, as demonstrated by its inclusion among several ceRNAs regulating miR‐802 in diverse malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its roles in hematological malignancy, metabolic disorders, and various solid tumors including gastric, breast, and tongue cancers, IGFL2 also appears in the tumor microenvironment. For instance, it is part of a 12‐marker panel associated with cancer‐associated fibroblasts in hepatocellular carcinoma, suggesting it may contribute to the remodeling of the tumor stroma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Similarly, in the context of mitochondrial dysfunction, IGFL2 expression is downregulated in human skin fibroblasts, aligning with a broader suppression of growth factors and cytokines that protect against apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, IGFL2‐AS1 has also been identified as a prognostic biomarker in colon adenocarcinoma, where its high expression correlates with enhanced epithelial‐mesenchymal transition and worse clinical outcomes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", as well as in clear cell renal cell carcinoma, where it forms part of a panel of candidate lncRNAs with diagnostic and prognostic value."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, both IGFL2 and IGFL2‐AS1 are emerging as multifaceted regulators with potential roles in modulating cell proliferation, survival, migration, and metabolic processes. Their dysregulation in various cancers and metabolic disorders underlines their promise as diagnostic biomarkers and as targets for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N Booken, A Gratchev, J Utikal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.leu.2405044"}], "href": "https://doi.org/10.1038/sj.leu.2405044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18033314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18033314"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Siqi Ge, Youxin Wang, Manshu Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type 2 Diabetes Mellitus: Integrative Analysis of Multiomics Data for Biomarker Discovery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "OMICS (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/omi.2018.0053"}], "href": "https://doi.org/10.1089/omi.2018.0053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30004843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30004843"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhilong Lin, Yuanliang Zhang, Huozhen Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative Strategy To Explore Missing Proteins with Low Molecular Weight."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.jproteome.9b00353"}], "href": "https://doi.org/10.1021/acs.jproteome.9b00353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31592669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31592669"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yu Ma, Yi Liu, Yan-Song Pu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA IGFL2-AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR-802 in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.23155"}], "href": "https://doi.org/10.1002/mc.23155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31943339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31943339"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haixia Wang, Yujie Shi, Chuan-Huizi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLF5-induced lncRNA IGFL2-AS1 promotes basal-like breast cancer cell growth and survival by upregulating the expression of IGFL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.04.016"}], "href": "https://doi.org/10.1016/j.canlet.2021.04.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34052325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34052325"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chongyang Ren, Xiaojiang Tang, Haitao Lan "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PeerJ (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7717/peerj.11377"}], "href": "https://doi.org/10.7717/peerj.11377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33987034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33987034"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ruimin Zhao, Shiyang Wang, Lu Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IGFL2-AS1 facilitates tongue squamous cell carcinoma progression via Wnt/β-catenin signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oral Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/odi.13935"}], "href": "https://doi.org/10.1111/odi.13935"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34085359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34085359"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tong Gao, Mengsha Zou, Tiancheng Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysfunction of miR-802 in tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lab Anal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcla.23989"}], "href": "https://doi.org/10.1002/jcla.23989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34558723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34558723"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Baojia Zou, Xialei Liu, Yihang Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel 12-marker panel of cancer-associated fibroblasts involved in progression of hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Manag Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/CMAR.S176152"}], "href": "https://doi.org/10.2147/CMAR.S176152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30464627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30464627"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Vladimir N Ivanov, Shanaz A Ghandhi, Hongning Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: a role for NF-κB-STAT3-directed gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2011.03.012"}], "href": "https://doi.org/10.1016/j.yexcr.2011.03.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21440540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21440540"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaoning Cen, Yunmei Huang, Zhuangnian Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA IGFL2-AS1 Promotes the Proliferation, Migration, and Invasion of Colon Cancer Cells and is Associated with Patient Prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Manag Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/CMAR.S313775"}], "href": "https://doi.org/10.2147/CMAR.S313775"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34377016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34377016"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kirsten M Tracy, Coralee E Tye, Natalie A Page, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective expression of long non-coding RNAs in a breast cancer cell progression model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.25997"}], "href": "https://doi.org/10.1002/jcp.25997"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28488769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28488769"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Gong Cheng, Di Liu, Huageng Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A cluster of long non-coding RNAs exhibit diagnostic and prognostic values in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.102407"}], "href": "https://doi.org/10.18632/aging.102407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31727869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31727869"}]}]}]}