{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA FOXC2‐AS1 has emerged as a multifunctional regulator that plays context‐dependent roles in human disease. In several cancers—including osteosarcoma, colorectal, prostate, gastric, melanoma, tongue squamous cell carcinoma, and non‐small cell lung cancer—FOXC2‐AS1 is frequently upregulated and associated with poor prognosis. In these settings, FOXC2‐AS1 promotes oncogenesis and chemoresistance by enhancing cell proliferation, migration, invasion, and metastasis. Mechanistically, it often acts by stabilizing its sense transcript FOXC2 through the formation of RNA duplexes and by recruiting epigenetic modifiers (such as NSUN2 and EZH2) to modulate gene expression. Moreover, FOXC2‐AS1 can function as a competing endogenous RNA that sponges microRNAs (e.g., miR‐1253 and miR‐6868‐5p), thereby suppressing tumor‐suppressive targets (such as p15) and indirectly promoting the expression of oncogenic factors (for instance, EZH2 or E2F3)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In non‐malignant contexts, FOXC2‐AS1 also regulates cellular and tissue homeostasis. For example, in atherosclerosis it is upregulated in vascular smooth muscle cells where, through a miR‐1253/FOXF1 signaling axis, it promotes proliferation and protects against apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In human adipocytes, FOXC2‐AS1 enhances the browning of white adipose tissue and boosts thermogenic capacity via pathways involving autophagy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, in the context of doxorubicin‐induced cardiotoxicity, FOXC2‐AS1 appears to exert a protective effect by upregulating WISP1 to improve cardiomyocyte viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Similarly, in varicose veins, FOXC2‐AS1 facilitates phenotypic switching, proliferation, and migration of smooth muscle cells by activating a FOXC2‐Notch signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, the diverse functions of FOXC2‐AS1—from enhancing oncogenic behaviors and drug resistance via transcriptional and post‐transcriptional regulation, to modulating cell survival and differentiation in non‐cancerous tissues—highlight its potential as both a prognostic biomarker and a therapeutic target across a range of human pathologies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chun-Lin Zhang, Kun-Peng Zhu, Xiao-Long Ma "}, {"type": "b", "children": [{"type": "t", "text": "Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2017.03.018"}], "href": "https://doi.org/10.1016/j.canlet.2017.03.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28323030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28323030"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ke Pan, Yong Xie "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FOXC2-AS1 enhances FOXC2 mRNA stability to promote colorectal cancer progression via activation of Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-FAK signal pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-2633-7"}], "href": "https://doi.org/10.1038/s41419-020-2633-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32513911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32513911"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yanbo Chen, Meng Gu, Chong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA FOXC2-AS1 facilitates the proliferation and progression of prostate cancer via targeting miR-1253/EZH2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2018.10.085"}], "href": "https://doi.org/10.1016/j.gene.2018.10.085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30389560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30389560"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jijun Yan, Juntao Liu, Zhengbin Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-021-00583-3"}], "href": "https://doi.org/10.1007/s13577-021-00583-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34324140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34324140"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "D-F Xu, X-H Tao, Y Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FOXC2-AS1 stimulates proliferation of melanoma via silencing p15 by recruiting EZH2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202009_22835"}], "href": "https://doi.org/10.26355/eurrev_202009_22835"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32964984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32964984"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Cuiting Chen, Qiongyu Chen, Jian Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H3K27ac-induced FOXC2-AS1 accelerates tongue squamous cell carcinoma by upregulating E2F3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Oral Pathol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jop.13232"}], "href": "https://doi.org/10.1111/jop.13232"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34358374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34358374"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhe Sun, Chaozhu He, Miao Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FOXC2 antisense transcript accelerates non-small-cell lung cancer tumorigenesis via silencing p15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Transl Res (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31396359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31396359"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Y-Q Wang, Z-M Xu, X-L Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FOXC2-AS1 regulated proliferation and apoptosis of vascular smooth muscle cell through targeting miR-1253/FOXF1 axis in atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202003_20698"}], "href": "https://doi.org/10.26355/eurrev_202003_20698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32271448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32271448"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yan Wang, Siyu Hua, Xianwei Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Effect of FOXC2-AS1 on White Adipocyte Browning and the Possible Regulatory Mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Endocrinol (Lausanne) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fendo.2020.565483"}], "href": "https://doi.org/10.3389/fendo.2020.565483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33193083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33193083"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shenwei Zhang, Yiqiang Yuan, Zheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FOXC2-AS1 protects cardiomyocytes from doxorubicin-induced cardiotoxicity through activation of WNT1-inducible signaling pathway protein-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Biotechnol Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/09168451.2018.1553606"}], "href": "https://doi.org/10.1080/09168451.2018.1553606"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30558506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30558506"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Chuang Zhang, Huixiang Li, Xueli Guo "}, {"type": "b", "children": [{"type": "t", "text": "FOXC2-AS1 regulates phenotypic transition, proliferation and migration of human great saphenous vein smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40659-019-0266-z"}], "href": "https://doi.org/10.1186/s40659-019-0266-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31801629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31801629"}]}]}]}