Genetic predisposition of SNPs in miRNA-149 (rs2292832) and FOXE1 (rs3758249) in thyroid Cancer

Mol Biol Rep. 2021 Dec;48(12):7801-7809. doi: 10.1007/s11033-021-06795-y. Epub 2021 Oct 13.

Abstract

Background: Many efforts have been made in recent years to investigate the alterations in protein-coding genes as well as non-coding RNAs that are playing an emerging role in the development and progression of cancers. These miRNAs are short non-coding functional RNAs that are involved in the regulation of transcriptome. In different studies, it was found that human miRNA-149 is an important microRNA that is functioning either as onco-miRNAs or acting as tumor suppressors, in different conditions.

Rationale: Many of the miRNAs are regulating different SNPs of FOXE1 in different studies which are causing low-to-moderate penetrance of genes that initiates the development of thyroid cancer. The involvement of SNPs in miRNA-149 gene rs2292832 and FOXE1 rs3758249 with PTC for better disease prognosis and management was determined in this study and the relation between these SNPs at the genotypic level was also evaluated. MATERIALS AND METHODS: PTC patients with age and gender-matched controls were recruited in the present study. Blood samples were collected in EDTA vacutainer followed by DNA extraction by the organic method. Genotyping of rs2292832 and rs3758249 was done by ARMS-PCR and PCR- RFLP respectively. Statistical analyses were carried out by using SPSS software (version 20).

Results: The mutation T>C in miRNA-149 rs2292832 was significantly associated with thyroid cancer (p-value 0.0004, < 0.05) while rs3758249 G>C did not show significant association with the disease (p-value 0.124244, > 0.05). Moreover, no correlation of rs2292832 at the genotype level was observed with rs3758249.

Conclusions: miRNA-149 gene SNP rs2292832 was observed in strong association with thyroid cancer. Lack of genetic association of rs3758249 of FOXE1 gene has been ruled for the disease. The statistically significant association of rs2292832 with thyroid cancer depicts its mechanistic involvement at the cellular level in Papillary Thyroid Carcinoma.

Keywords: FOXE1; Papillary thyroid carcinoma; Thyroid cancer; miRNA-149; rs2292832; rs3758249.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Carcinoma, Papillary / genetics
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Pakistan
  • Polymorphism, Single Nucleotide / genetics
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Neoplasms / genetics*

Substances

  • FOXE1 protein, human
  • Forkhead Transcription Factors
  • MIRN149 microRNA, human
  • MicroRNAs