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<p>Genome-wide association studies (GWASs) have revealed the lung cancer susceptibility-associated non-coding SNP rs17728461 C/G. In this study, we demonstrated that rs17728461 is also associated with lung cancer outcome. The risk G allele increases the proliferative index and motility of cancer cells and promotes cancer metastasis in vivo in a xenograft mouse model. Mechanistically, rs17728461-G establishes a physical interchromosomal interaction between the rs17728461-bearing DNA fragment and the <i>RAB27A</i> gene locus and thereby increases RAB27A expression and promotes subsequent exosome secretion. eQTL analysis and immunostaining revealed an association between rs17728461-G and increased RAB27A expression in human lung cancers. These findings reveal a noncoding SNP-mediated interchromosomal regulatory mechanism underlying lung cancer progression.</p>

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Noncoding SNP rs17728461 modulates lung cancer progression via interchromosomal regulation of RAB27A expression

  • 期刊论文

  • 发表日期：

    2026年6月2日

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  • Yan Jin,
  • Xiaoling Tian,
  • Wenxu Liu,
  • Bing Guo,
  • Xinyue Lei,
  • Xinhua Liu,
  • Guoli Li,
  • Xujing Liu,
  • Zengtuan Xiao,
  • Mengzhe Zhang,
  • Yuxin Fan,
  • Zhenfa Zhang,
  • Zhenyi Ma,
  • Zhe Liu

摘要

Genome-wide association studies (GWASs) have revealed the lung cancer susceptibility-associated non-coding SNP rs17728461 C/G. In this study, we demonstrated that rs17728461 is also associated with lung cancer outcome. The risk G allele increases the proliferative index and motility of cancer cells and promotes cancer metastasis in vivo in a xenograft mouse model. Mechanistically, rs17728461-G establishes a physical interchromosomal interaction between the rs17728461-bearing DNA fragment and the RAB27A gene locus and thereby increases RAB27A expression and promotes subsequent exosome secretion. eQTL analysis and immunostaining revealed an association between rs17728461-G and increased RAB27A expression in human lung cancers. These findings reveal a noncoding SNP-mediated interchromosomal regulatory mechanism underlying lung cancer progression.