| Autor: |
Murugan, Avaniyapuram Kannan, Al-Hindi, Hindi, Alzahrani, Ali S. |
| Zdroj: |
Endocrine; 20240101, Issue: Preprints p1-11, 11p |
| Abstrakt: |
Purpose: Long noncoding RNAs (lncRNAs) play an essential role in the epigenetic regulation of various key genes involved in vital cellular functions. A somatic dinucleotide mutation in the lncRNA GAS8-AS1was reported in Chinese papillary thyroid cancer. However, GAS8-AS1dinucleotide alteration and its impact have never been explored in differentiated thyroid cancers and other populations. Methods: We extracted genomic DNA from 265 DTCs and 97 normal healthy subjects, PCR amplified and Sanger sequenced to examine the GAS8-AS1dinucleotide alteration. Calculated genotype/allele frequency to test Hardy-Weinberg Equilibrium (HWE) and performed a genetic model of inheritance to determine its association with DTC risk. Correlated the GAS8-AS1dinucleotide variant distribution with clinical characteristics to find the association. Predicted GAS8-AS1RNA secondary structure for wild type and variant using RemuRNA and RNAfold to assess the conformational changes. Results: GAS8-AS1dinucleotide alteration (n.713A > G, rs55742939; n.714T > C, rs61118444) identified in DTCs is a germline variant not somatic. The GAS8-AS1genotype and allele frequency significantly deviated for HWE in DTCs (χ2 = 37.954; p= 0.0001) though not associated with its risk. Dinucleotide variant distribution was remarkably associated with early-stage disease (p= 0.002), lymph node (p= 0.01), and distant metastasis (p= 0.01) in DTCs. The GAS8-AS1bearing dinucleotide variant markedly showed conformational change compared to that of its wild type. Conclusions: These findings indicate that GAS8-AS1is genetically deregulated and implicated in several stages of DTC tumorigenesis suggesting it could be a promising prognostic biomarker in DTCs. |
| Databáze: |
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