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Genetic predisposition of SNPs in miRNA-149 (rs2292832) and FOXE1 (rs3758249) in thyroid Cancer
Rashida Khan1,2, Humaira Shaheen1, Qaisar Mansoor2
1Department of Zoology, PMAS-Arid Agriculture University, Rawalpindi, Pakistan.
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.
Insights
The miRNA-149 gene SNP rs2292832 is strongly associated with thyroid cancer, indicating its role in papillary thyroid carcinoma development. The FOXE1 gene SNP rs3758249 showed no significant association with the disease.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) are crucial non-coding RNAs regulating gene expression and implicated in cancer.
- miRNA-149 functions as either an onco-miRNA or tumor suppressor, depending on the cellular context.
- Single Nucleotide Polymorphisms (SNPs) in miRNA genes can influence cancer susceptibility and progression.
Purpose of the Study:
- To investigate the association of miRNA-149 gene SNP rs2292832 and FOXE1 gene SNP rs3758249 with papillary thyroid cancer (PTC).
- To evaluate the potential of these SNPs for disease prognosis and management.
- To explore the genotypic correlation between rs2292832 and rs3758249 in PTC patients.
Main Methods:
- Case-control study involving PTC patients and age/gender-matched controls.
- DNA extraction from blood samples using the organic method.
- Genotyping performed using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) for rs2292832 and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) for rs3758249.
- Statistical analysis conducted using SPSS software.
Main Results:
- A significant association was found between the T>C mutation in miRNA-149 rs2292832 and thyroid cancer (p=0.0004).
- The G>C mutation in FOXE1 rs3758249 did not show a significant association with thyroid cancer (p=0.124).
- No significant correlation was observed between the genotypes of rs2292832 and rs3758249.
Conclusions:
- The miRNA-149 gene SNP rs2292832 is strongly associated with thyroid cancer, suggesting a mechanistic role in papillary thyroid carcinoma.
- The FOXE1 gene SNP rs3758249 is not genetically associated with thyroid cancer.
- These findings highlight the potential of miRNA-149 genetic variants as biomarkers for thyroid cancer.
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