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Novel functional variants in the Notch pathway and survival of Chinese colorectal cancer.

Publication ,  Journal Article
Qu, X; Zhao, L; Wang, M; Zhang, R; Cheng, L; Qiu, L; Tong, X; Cai, S; Wei, Q; Li, Q
Published in: Int J Cancer
July 1, 2021

Notch signaling pathway plays crucial roles in progression of colorectal cancer (CRC), likely affecting overall survival (OS). In a two-stage survival analysis of 1116 CRC patients in East China, we found that one locus at MINAR1 out of 133 genes in the Notch signaling pathway was significantly associated with OS (P < 1 × 10-6 , false discovery rate < 0.01). This locus containing seven single-nucleotide polymorphisms (SNPs) in high linkage disequilibrium (R2 = 1) is located on chromosome 15, of which the MINAR1 rs72430409 G allele was associated with a greater death risk (HR = 1.98, 95% CI = 1.55-2.54, P = 6.8 × 10-8 ). Further analysis of ChIP-sequencing data from the encyclopedia of DNA Elements showed that rs72430409 and rs72630408 were potential cis-regulatory elements for the MINAR1 promoter. Additional expression quantitative trait loci analysis revealed that rs72430409 G>A and rs72630408 A>G were correlated with increased MINAR1 expression levels in both blood cells and colon tissues. Dual luciferase assays revealed that the rs72430409 A allele increased MINAR1 promoter activity. The Cancer Genome Atlas data showed that expression levels of MINAR1 in CRC samples were significantly higher than that in normal colorectal tissue and that high expression of MINAR1 was associated with a shortened OS, likely via activating the epithelial mesenchymal transition (EMT) pathway as shown in the gene-set enrichment analysis. In vitro, RNAi-mediated silencing of MINAR1 led to decreased migration and proliferation in CRC cancer cells, and MINAR1 silencing could downregulate the expression of key effector genes in EMT and glycolysis. Larger cohort studies and further experiments are needed to validate our findings.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

July 1, 2021

Volume

149

Issue

1

Start / End Page

84 / 96

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Survival Rate
  • Retrospective Studies
  • Receptors, Cell Surface
  • Receptor, Notch1
  • Quantitative Trait Loci
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
 

Citation

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Qu, X., Zhao, L., Wang, M., Zhang, R., Cheng, L., Qiu, L., … Li, Q. (2021). Novel functional variants in the Notch pathway and survival of Chinese colorectal cancer. Int J Cancer, 149(1), 84–96. https://doi.org/10.1002/ijc.33561
Qu, Xiaofei, Liqin Zhao, Mengyun Wang, Ruoxin Zhang, Lei Cheng, Lixin Qiu, Xiaoxia Tong, Sanjun Cai, Qingyi Wei, and Qingguo Li. “Novel functional variants in the Notch pathway and survival of Chinese colorectal cancer.Int J Cancer 149, no. 1 (July 1, 2021): 84–96. https://doi.org/10.1002/ijc.33561.
Qu X, Zhao L, Wang M, Zhang R, Cheng L, Qiu L, et al. Novel functional variants in the Notch pathway and survival of Chinese colorectal cancer. Int J Cancer. 2021 Jul 1;149(1):84–96.
Qu, Xiaofei, et al. “Novel functional variants in the Notch pathway and survival of Chinese colorectal cancer.Int J Cancer, vol. 149, no. 1, July 2021, pp. 84–96. Pubmed, doi:10.1002/ijc.33561.
Qu X, Zhao L, Wang M, Zhang R, Cheng L, Qiu L, Tong X, Cai S, Wei Q, Li Q. Novel functional variants in the Notch pathway and survival of Chinese colorectal cancer. Int J Cancer. 2021 Jul 1;149(1):84–96.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

July 1, 2021

Volume

149

Issue

1

Start / End Page

84 / 96

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Survival Rate
  • Retrospective Studies
  • Receptors, Cell Surface
  • Receptor, Notch1
  • Quantitative Trait Loci
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged