Identifying putative causal links between serum circulating microRNAs and thyroid cancer using Mendelian...

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Thyroid cancer incidence is rising globally.
• Understanding risk factors is crucial for early detection and prevention.
• Serum circulating microRNAs (miRNAs) are potential novel biomarkers.

Purpose of the Study:

• To investigate the causal relationship between serum circulating miRNAs and thyroid cancer risk.
• To identify specific miRNAs associated with increased or decreased thyroid cancer susceptibility.
• To explore the underlying biological pathways involved.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis.
• Utilized miRNA expression quantitative trait loci (eQTL) and thyroid cancer genome-wide association study (GWAS) data.
• Applied inverse variance-weighted (IVW) and MR-Egger methods; performed target gene and pathway analysis.

Main Results:

• Identified three miRNAs significantly associated with thyroid cancer risk: miR-hsa-125b-5p and miR-hsa-30a-3p (harmful), and miR-hsa-130a-3p (protective).
• Findings were consistent across discovery and validation cohorts.
• Enrichment analysis revealed involvement in gland development, cell senescence, and signaling pathways (FoxO, p53).

Conclusions:

• Specific serum miRNAs show potential causal associations with thyroid cancer risk.
• miR-hsa-125b-5p, miR-hsa-30a-3p, and miR-hsa-130a-3p warrant further investigation.
• These miRNAs could serve as potential biomarkers for thyroid cancer risk prediction and early diagnosis.