{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The long non‐coding RNA CASC8, located at the 8q24 locus, has emerged as a multifunctional player in diverse human diseases, particularly cancers. Genetic association studies have identified several CASC8 single nucleotide polymorphisms (SNPs)—including rs10505477, rs7014346, rs6983267, rs1447295, and rs1562430—that are linked with altered susceptibility to multiple cancers such as lung, colorectal, prostate, esophageal, gallbladder, and pancreatic cancers, as well as with anthropometric traits in different ethnic groups."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In lung cancer, for instance, the rs10505477 polymorphism has been associated not only with disease risk in specific subgroups but also with response and toxicity profiles for platinum‐based chemotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role as a genetic marker, emerging functional evidence indicates that CASC8 may actively modulate tumor biology. In bladder cancer, reduced CASC8 expression correlates with advanced disease; experimental restoration of CASC8 levels suppresses cell proliferation by interacting with fibroblast growth factor receptor 1 (FGFR1) to inhibit lactate dehydrogenase A phosphorylation, thereby attenuating glycolysis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In pancreatic adenocarcinoma, high CASC8 expression has been linked with poor patient prognosis and appears to participate in competitive endogenous RNA (ceRNA) networks involving factors such as H19, miR‑671, and SMAD7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in gastric cancer, CASC8 polymorphisms have been associated with unfavorable survival outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CASC8 variants have been implicated as potential non‐invasive biomarkers not only for oncologic risk assessment but also for other conditions, including coronary heart disease and tuberculosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In prostate cancer, CASC8 risk alleles at the 8q24 region contribute to inherited susceptibility and, when combined with other risk variants, help stratify patient risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CASC8 appears to function through dual mechanisms: as a genetic biomarker influencing cancer risk, prognosis, and treatment response, and as a molecular regulator that can modulate key cellular pathways such as glycolysis and ceRNA networks in a tissue‐specific manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maggie C Y Ng, Mariaelisa Graff, Yingchang Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1006719"}], "href": "https://doi.org/10.1371/journal.pgen.1006719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28430825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28430825"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lei Hu, Shu-Hui Chen, Qiao-Li Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Environ Res Public Health (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijerph13060545"}], "href": "https://doi.org/10.3390/ijerph13060545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27249003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27249003"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kunhou Yao, Long Hua, Lunshou Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000001884"}], "href": "https://doi.org/10.1097/MD.0000000000001884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26579801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26579801"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yonghua Sang, Haiyong Gu, Yongbing Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA CASC8 polymorphisms are associated with the risk of esophageal cancer in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thorac Cancer (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1759-7714.13612"}], "href": "https://doi.org/10.1111/1759-7714.13612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32875717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32875717"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Renguang Hu, Peng Zhong, Lu Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long Noncoding RNA Cancer Susceptibility Candidate 8 Suppresses the Proliferation of Bladder Cancer Cells via Regulating Glycolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2017.3785"}], "href": "https://doi.org/10.1089/dna.2017.3785"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28759252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28759252"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yingyi Wang, Yuemei Yang, Yanfeng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High Cancer Susceptibility Candidate 8 Expression Is Associated With Poor Prognosis of Pancreatic Adenocarcinoma: Validated Analysis Based on Four Cancer Databases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2020.00392"}], "href": "https://doi.org/10.3389/fcell.2020.00392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32582694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32582694"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wenjuan Zhu, Wenzhe Gao, Yanyao Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and Development of Long Non-coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Onco Targets Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/OTT.S265036"}], "href": "https://doi.org/10.2147/OTT.S265036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33262608"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33262608"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yangyu Zhang, Yanhua Wu, Zhifang Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA polymorphisms on 8q24 are associated with the prognosis of gastric cancer in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PeerJ (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7717/peerj.8600"}], "href": "https://doi.org/10.7717/peerj.8600"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32117633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32117633"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yan Lu, Wei Yuan, Lan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of lncRNA CASC8, CASC11, and PVT1 Genetic Variants to the Susceptibility of Coronary Heart Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cardiovasc Pharmacol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FJC.0000000000001019"}], "href": "https://doi.org/10.1097/FJC.0000000000001019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34001726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34001726"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Guoye Liu, Rui Xia, Qian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Significance of LncRNA CASC8 genetic polymorphisms on the tuberculosis susceptibility in Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lab Anal (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcla.23234"}], "href": "https://doi.org/10.1002/jcla.23234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32034808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32034808"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Csilla Sipeky, Teuvo L J Tammela, Anssi Auvinen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel prostate cancer susceptibility gene SP6 predisposes patients to aggressive disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate Cancer Prostatic Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41391-021-00378-5"}], "href": "https://doi.org/10.1038/s41391-021-00378-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34012061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34012061"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yan Gu, Xiaozeng Lin, Anil Kapoor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Oncogenic Potential of the Centromeric Border Protein FAM84B of the 8q24.21 Gene Desert."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes11030312"}], "href": "https://doi.org/10.3390/genes11030312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32183428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32183428"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Monir Sadat Haerian, Batoul Sadat Haerian, Saadat Molanaei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of association of CASC8 rs1447295 with colorectal cancer in Iranian population: A multicenter case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2017.08.042"}], "href": "https://doi.org/10.1016/j.gene.2017.08.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28887158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28887158"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Saurabh Yadav, Abhijit Chandra, Ashok Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of TERT-CLPTM1L and 8q24 Common Genetic Variants with Gallbladder Cancer Susceptibility and Prognosis in North Indian Population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10528-018-9843-z"}], "href": "https://doi.org/10.1007/s10528-018-9843-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29450669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29450669"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Mohammad Hashemi, Gholamreza Bahari, Majid Naderi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of lnc-LAMC2-1:1 rs2147578 and CASC8 rs10505477 Polymorphisms with Risk of Childhood Acute Lymphoblastic Leukemia"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian Pac J Cancer Prev (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.22034/APJCP.2016.17.11.4985"}], "href": "https://doi.org/10.22034/APJCP.2016.17.11.4985"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28032728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28032728"}]}]}]}