Genetic predisposition to papillary thyroid carcinoma is mediated by a long non-coding RNA TINCR enhancer...

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Single nucleotide polymorphisms (SNPs) in regulatory regions can alter gene expression and disease risk.
• Papillary thyroid carcinoma (PTC) is a common endocrine malignancy.
• The terminal differentiation-induced non-coding RNA (TINCR) gene plays a role in cellular processes.

Purpose of the Study:

• To investigate the association between the rs8101923 SNP in the TINCR gene and the risk of papillary thyroid carcinoma (PTC).
• To elucidate the functional impact of rs8101923 on TINCR expression, enhancer activity, and its role in PTC pathogenesis.

Main Methods:

• Genotyping of rs8101923 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 559 PTC patients and 445 controls.
• Quantitative real-time PCR and dual-luciferase reporter assays to assess TINCR expression and enhancer activity.
• Chromatin immunoprecipitation (ChIP) to determine transcription factor AP-2α binding to the TINCR enhancer.

Main Results:

• The G allele of rs8101923 was significantly associated with an increased risk of PTC (adjusted OR = 1.37; 95% CI: 1.15-1.64).
• rs8101923 was found to increase TINCR transcriptional levels and enhancer activity (P < 0.05).
• Transcription factor AP-2α binds to the TINCR enhancer at the rs8101923 locus and promotes PTC cell proliferation.

Conclusions:

• The rs8101923 SNP is a risk factor for papillary thyroid carcinoma.
• This SNP influences TINCR expression and enhancer activity, mediated by AP-2α binding, contributing to PTC pathogenesis.
• Findings provide mechanistic insights into how rs8101923 predisposes individuals to PTC.