A genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m6A modification

  • 0Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao, Gulou District, Nanjing, 210009, China.

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Summary

This summary is machine-generated.

Genetic variants influence N6-methyladenosine (m<sup>6</sup>A) levels, impacting cervical cancer (CC) risk. A specific variant, rs1059288 in TAPBP, increases CC susceptibility by altering m<sup>6</sup>A modification, promoting tumor growth and drug resistance.

Area Of Science

  • Genetics
  • Oncology
  • Molecular Biology

Background

  • Genetic variants can alter N6-methyladenosine (m<sup>6</sup>A) levels, influencing gene expression and disease susceptibility.
  • Understanding the role of m<sup>6</sup>A-associated genetic variants in cervical cancer (CC) is crucial for improving screening and treatment strategies.

Purpose Of The Study

  • To identify and characterize m<sup>6</sup>A-associated single nucleotide polymorphisms (SNPs) linked to cervical cancer risk.
  • To elucidate the functional and mechanistic role of the identified risk SNP in CC development and progression.

Main Methods

  • Genome-wide analysis of m<sup>6</sup>A-associated SNPs using TCGA and JENGER databases with RNA-seq and MeRIP-seq data.
  • Case-control study validation of the risk SNP rs1059288 in a cohort of 921 CC cases and 1077 controls.
  • In vitro experiments assessing TAPBP's role in CC cell growth, migration, apoptosis, and drug resistance, including pathway analysis.

Main Results

  • The SNP rs1059288 (A>G) in the TAPBP 3' UTR was significantly associated with increased CC risk (OR 1.48).
  • The risk G allele correlated with elevated m<sup>6</sup>A modification of TAPBP, facilitated by METTL14 and YTHDF2.
  • Overexpression of TAPBP in CC tissues promoted tumor growth, migration, and chemoresistance, while inhibiting apoptosis and affecting the JAK/STAT/MICB pathway.

Conclusions

  • Genetic variation rs1059288 contributes to cervical cancer susceptibility through altered m<sup>6</sup>A modification of TAPBP.
  • TAPBP overexpression drives CC progression and confers drug resistance, highlighting its potential as a therapeutic target.
  • Targeting TAPBP or related pathways may offer novel strategies for cervical cancer treatment and prevention.

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