LncRNA GAS8-AS1 dinucleotide genetic variant

DTC Dinucleotide variant GAS8-AS1 Mutation Thyroid cancer lncRNA

Journal

Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444

Informations de publication

Date de publication:
05 Apr 2024
Historique:
received: 31 01 2024
accepted: 24 03 2024
medline: 6 4 2024
pubmed: 6 4 2024
entrez: 5 4 2024
Statut: aheadofprint

Résumé

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-AS1 was reported in Chinese papillary thyroid cancer. However, GAS8-AS1 dinucleotide alteration and its impact have never been explored in differentiated thyroid cancers and other populations. We extracted genomic DNA from 265 DTCs and 97 normal healthy subjects, PCR amplified and Sanger sequenced to examine the GAS8-AS1 dinucleotide 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-AS1 dinucleotide variant distribution with clinical characteristics to find the association. Predicted GAS8-AS1 RNA secondary structure for wild type and variant using RemuRNA and RNAfold to assess the conformational changes. GAS8-AS1 dinucleotide alteration (n.713A > G, rs55742939; n.714T > C, rs61118444) identified in DTCs is a germline variant not somatic. The GAS8-AS1 genotype 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-AS1 bearing dinucleotide variant markedly showed conformational change compared to that of its wild type. These findings indicate that GAS8-AS1 is genetically deregulated and implicated in several stages of DTC tumorigenesis suggesting it could be a promising prognostic biomarker in DTCs.

Identifiants

DOI: 10.1007/s12020-024-03802-7 PMID: 38580894
pubmed: 38580894
doi: 10.1007/s12020-024-03802-7
pii: 10.1007/s12020-024-03802-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Avaniyapuram Kannan Murugan (AK)

Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia. akmurugan@gmail.com.

Hindi Al-Hindi (H)

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.

Ali S Alzahrani (AS)

Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia. aliz@kfshrc.edu.sa.
Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia. aliz@kfshrc.edu.sa.

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