MALAT1 rs619586 polymorphism functions as a prognostic biomarker in the management of differentiated thyroid...

This study aimed to explore the roles of miR-214 and MALAT1 rs619586 polymorphism in the control and survival of differentiated thyroid carcinoma (DTC) via Cox regression analyses. The levels of MALAT1, miR-214, and CTNNB1 in different experimental groups were compared to study the interaction among MALAT1, miR-214, and CTNNB1. MTT and colony assays were used to investigate the role of rs619586 polymorphism in cell growth. The G allele of rs619586 polymorphism obviously decreased the 5-year survival of patients with DTC. Additionally, compared with AA-genotyped patients, patients carrying the AG/GG genotypes of MALAT1 rs619586 polymorphism showed much higher levels of DTC grade and CTNNB1 expression, along with lower levels of MALAT1 and miR-214 expression. Furthermore, the transcription activity of MALAT1 was significantly lowered by the rs619586G allele or miR-214 mimic, while the miR-214 inhibitor upregulated the luciferase activity of MALAT1. Additionally, miR-214 inhibited CTNNB1 expression by targeting CTNNB1 3'-untranslated region. Finally, the G allele of MALAT1 rs619586 polymorphism apparently promoted cell proliferation. Our study indicated that miR-214 inhibited MALAT1 expression by directly binding to the G allele of MALAT1 rs619586 polymorphism, thus inhibiting CTNNB1 expression and promoting cell proliferation in the pathogenesis of DTC. Therefore, MALAT1 rs619586 polymorphism could be used to predict the prognosis of DTC.