rs2357322 and rs17726078 Contribute to Breast Cancer Risk by Regulating DLX2 Expression.

Background and Aims: Breast cancer is the most abundant cancer type in female. Genome‐wide association study suggests that rs2016394, one SNP at the intron of DLX2 divergent transcript (DLX2-DT), is significantly associated with this disease. Through 1000 genomes project data analysis, it is observe...

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Publicado en:Breast Journal Vol. 2026; pp. 1 - 9
Autores principales: Zhang, Xin-Xin, Guo, Hao, Li, Hai-Yan, Zhou, Xi-Ting, Song, Hong-Li, Xu, Jiang-Wei, Fu, Yu-Hang, Tian, Ru-Hui, Jiang, Ru, Liu, Chun-Chun, Sun, Chang, Sharma, Karuna
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 8/14/2026
Acceso en línea:Ver este registro en EBSCOhost
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        10.1155/tbj/3096873
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        atl: rs2357322 and rs17726078 Contribute to Breast Cancer Risk by Regulating DLX2 Expression.
      aug:
        au:
          Zhang, Xin-Xin
          Guo, Hao
          Li, Hai-Yan
          Zhou, Xi-Ting
          Song, Hong-Li
          Xu, Jiang-Wei
          Fu, Yu-Hang
          Tian, Ru-Hui
          Jiang, Ru
          Liu, Chun-Chun
          Sun, Chang
          Sharma, Karuna
        affil: College of Life Sciences, , Shaanxi Normal University, , Xi'an Shaanxi, 710119, , China, snnu.edu.cn
      sug:
        subj:
          Gene Expression
          Breast Neoplasms Familial and Genetic
          Polymorphism, Single Nucleotide
          Breast Neoplasms Risk Factors
          Genomics
          Gene Editing
          Chromosome Mapping
          In Vitro Studies
          Genetic Techniques
          Descriptive Statistics
          Data Analysis Software
          T-Tests
          Cell Culture Techniques
          Reverse Transcriptase Polymerase Chain Reaction
          Mutation
          Funding Source
          Genome Wide Association Study
          Sequence Analysis
          Alleles
          Transcription Factors
          Oncogenes
          RNA, Messenger
          Cell Proliferation
          Wound Healing
      ab: Background and Aims: Breast cancer is the most abundant cancer type in female. Genome‐wide association study suggests that rs2016394, one SNP at the intron of DLX2 divergent transcript (DLX2-DT), is significantly associated with this disease. Through 1000 genomes project data analysis, it is observed that another three SNPs, rs743605, rs2357322, and rs17726078, show strong linkage disequilibrium with rs2016394. However, the functional SNP(s) and mechanism are still unknown. Methods: Functional genomics effort was performed for this locus. Results: Through luciferase assay, it is disclosed that rs743605 and rs2016394 are not with the ability to alter gene expression. In contrast, rs2357322 and rs17726078 alleles present significantly different luciferase expression, thus suggesting that these two SNPs are functional mutations. Chromosome conformation capture indicates that DLX2 (distal‐less Homeobox 2) can interact with the cis‐regulatory element containing these two SNPs and should be the regulatory target. Chromatin immunoprecipitation suggests that transcription factor MYC (MYC proto‐oncogene, bHLH transcription factor) can bind the rs17726078 surrounding region. Knock‐out of the segment containing these two SNPs by CRISPR/Cas9 can significantly increase DLX2 mRNA and protein expression, cell proliferation, colony formation, migration, and wound healing, thus suggesting that the cis‐regulatory element is an attenuator for gene expression. Conclusion: rs2357322 and rs17726078 might influence DLX2 expression and further contribute to breast cancer risk.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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