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Genetic variants in microRNAs are associated with cervical cancer risk

Shizhi Wang1, Haixia Zhu2, Bo Ding3

  • 1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.

Mutagenesis
|March 11, 2019
PubMed

Insights

Genetic variants in microRNAs (miRNAs) and their association with cervical cancer (CC) susceptibility were investigated. The miR-149 rs2292832 polymorphism was linked to an increased risk of CC, particularly in younger women and those with specific clinical factors.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Genetic variations in microRNAs (miRNAs) can impact their function.
  • Single-nucleotide polymorphisms (SNPs) in miRNAs are potential contributors to various diseases.
  • Cervical cancer (CC) susceptibility may be influenced by genetic factors.

Purpose of the Study:

  • To investigate the association between common miRNA single-nucleotide polymorphisms (SNPs) and cervical cancer (CC) susceptibility.
  • To identify specific miRNA SNPs that may increase the risk of developing CC.
  • To explore the functional impact of identified miRNA SNPs on miRNA processing and expression.

Main Methods:

  • Genotyping of common miRNA SNPs (miR-146a, miR-149, miR-196a2, miR-499, miR-605, miR-618) in 954 CC patients and 1339 controls.
  • Statistical analysis to determine the association between genotypes and CC risk, including subgroup analyses.
  • In vitro experiments using expression plasmids to assess the effect of miR-149 rs2292832 polymorphism on miRNA processing in HeLa and SiHa cells.

Main Results:

  • The miR-149 rs2292832 TC/CC genotypes showed a 21% increased risk of CC compared to the TT genotype (OR=1.21, 95% CI=1.00-1.47).
  • This association was more pronounced in subjects ≤ 48 years, with a history of abortion, premenopausal status, and stage II CC.
  • Expression analysis revealed that the C allele of rs2292832 led to higher mature miR-149-5p/3p transcription compared to the T allele.

Conclusions:

  • The miR-149 rs2292832 polymorphism is associated with an increased susceptibility to cervical cancer.
  • This SNP may influence CC risk by altering the processing of pre-miR-149 into mature miRNAs.
  • The findings highlight the role of miRNA genetic variations in cervical cancer pathogenesis.

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