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Genome-wide long non-coding RNA association study on Han Chinese women identifies lnchsat164 as a novel susceptibility gene for breast cancer

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Chinese Medical Journal 2021年第10期134卷 1138-1145页

作者： Jing-Kai Xu Guo-Zheng Li Zhi Li Wen-Jing Li Run-Sheng Chen Bo Zhang Xue-Jun Zhang Department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityKey Laboratory of DermatologyAnhui Medical UniversityMinistry of EducationHefeiAnhui 230032China Department of Genetics School of Life SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Oncology No.2 HospitalAnhui Medical UniversityHefeiAnhui 230032China Laboratory of Bioinformatics and Noncoding RNA Key Laboratory of RNA BiologyInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

Background:Single-nucleotide polymorphisms(SNPs)-associated genes and long non-coding RNAs(lncRNAs)can contribute to human disease.To comprehensively investigate the contribution of lncRNAs to breast cancer,we performed the first genome-wide lncRNA association study on Han Chinese women.Methods:We designed an lncRNA array containing>800,000 SNPs,which was incorporated into a 96-array plate by Affymetrix(CapitalBio Technology,China).Subsequently,we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals(5634 breast cancer patients and 6308 healthy controls).Additionally,in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.Results:We identified a novel breast cancer-associated susceptibility SNP,rs11066150(P_(meta)=2.34×10^(-8)),and a previously reported SNP,rs9397435(P_(meta)=4.32×10^(-38)),in Han Chinese women.rs11066150 is located in NONHSAT164009.1(lnchsat164),which is highly expressed in breast cancer tissues and cell lines.lnchsat164 overexpression promoted colony formation,whereas lnchsat164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.Conclusions:Based on our lncRNA array,we identified a novel breast cancer-associated lncRNA and found that lnchsat164 may contribute to breast cancer by regulating the cell cycle.These findings suggest a potential therapeutic target in breast cancer.

关键词： Breast cancer lnchsat164 Single-nucleotide polymorphisms

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