{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Circular RNA CDR1-AS (also known as ciRS-7) is an abundantly expressed, regulatory noncoding RNA that primarily exerts its function as a microRNA sponge, thereby modulating gene expression in diverse cellular contexts. In pancreatic islet cells, CDR1-AS sequesters miR-7 to relieve its inhibitory effects on targets such as Myrip and Pax6, leading to enhanced insulin secretion and improved β‐cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cardiomyocytes, increased CDR1-AS levels exacerbate myocardial infarction–induced apoptosis by sponging miR-7a, which in turn alters the expression of apoptotic mediators PARP and SP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, in periodontal ligament stem cells, CDR1-AS upregulation during osteogenic differentiation impedes miR-7 activity, thereby de-repressing growth differentiation factor 5 and promoting downstream Smad1/5/8 and p38 MAPK signaling essential for bone formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the oncologic setting, aberrant expression of CDR1-AS has been linked to tumor progression in several cancer types. For instance, in esophageal squamous cell carcinoma, CDR1-AS functions as a miRNA sponge for miR-876-5p to elevate MAGE-A family oncogene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In bladder cancer, CDR1-AS enhances cisplatin chemosensitivity by binding miR-1270, which leads to upregulation of the pro-apoptotic factor APAF1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, elevated levels of CDR1-AS in triple-negative breast cancer have been associated with increased cell migration and invasion, and in 5‑fluorouracil–resistant breast cancer, CDR1-AS modulates the miR-7/CCNE1 axis to affect chemoresponsiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In laryngeal squamous cell carcinoma, high CDR1-AS acts as a competing endogenous RNA to sequester miR-7, resulting in upregulation of oncogenes such as CCNE1 and PIK3CD and thereby promoting tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, in glioblastoma, deregulation of the miR-671-5p/CDR1-AS axis affects the expression of CDR1 and VSNL1, further implicating CDR1-AS in the modulation of tumor cell behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Notably, spatial expression studies in colon cancer reveal that CDR1-AS is absent from malignant epithelial cells yet highly expressed in the tumor stroma, highlighting a context-specific expression pattern and suggesting that its role as a microRNA sponge may be restricted to certain cellular compartments within the tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifaceted role of CDR1-AS as a microRNA sponge that modulates crucial signaling pathways involved in metabolic regulation, cardiac injury, osteogenesis, and cancer progression. The context-dependent functions of CDR1-AS not only illustrate its importance in normal physiology but also reveal its potential as a therapeutic target across a spectrum of human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huanyu Xu, Sen Guo, Wei Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep12453"}], "href": "https://doi.org/10.1038/srep12453"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26211738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26211738"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hai-Hua Geng, Rui Li, Ya-Min Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0151753"}], "href": "https://doi.org/10.1371/journal.pone.0151753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26998750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26998750"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaobei Li, Yunfei Zheng, Yan Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA CDR1as regulates osteoblastic differentiation of periodontal ligament stem cells via the miR-7/GDF5/SMAD and p38 MAPK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Res Ther (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13287-018-0976-0"}], "href": "https://doi.org/10.1186/s13287-018-0976-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30170617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30170617"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Meixiang Sang, Lingjiao Meng, Yang Sang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA ciRS-7 accelerates ESCC progression through acting as a miR-876-5p sponge to enhance MAGE-A family expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2018.03.049"}], "href": "https://doi.org/10.1016/j.canlet.2018.03.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29635069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29635069"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wenbo Yuan, Rui Zhou, Jingzi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA Cdr1as sensitizes bladder cancer to cisplatin by upregulating APAF1 expression through miR-1270 inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12523"}], "href": "https://doi.org/10.1002/1878-0261.12523"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31131537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31131537"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Meixiang Sang, Lingjiao Meng, Sihua Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA ciRS-7 Maintains Metastatic Phenotypes as a ceRNA of miR-1299 to Target MMPs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-18-0284"}], "href": "https://doi.org/10.1158/1541-7786.MCR-18-0284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30072582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30072582"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wei Yang, Juan Gu, Xuedong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of circular RNA CDR1as increases chemosensitivity of 5-FU-resistant BC cells through up-regulating miR-7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.14171"}], "href": "https://doi.org/10.1111/jcmm.14171"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30884120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30884120"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jianzhong Zhang, Huayong Hu, Yaoxin Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDR1as is overexpressed in laryngeal squamous cell carcinoma to promote the tumour's progression via miR-7 signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Prolif (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cpr.12521"}], "href": "https://doi.org/10.1111/cpr.12521"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30182381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30182381"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Davide Barbagallo, Angelo Condorelli, Marco Ragusa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6621"}], "href": "https://doi.org/10.18632/oncotarget.6621"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26683098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26683098"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Lasse S Kristensen, Karoline K Ebbesen, Martin Sokol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-18355-2"}], "href": "https://doi.org/10.1038/s41467-020-18355-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32917870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32917870"}]}]}]}