o:26354 Predictive significance of two MMP-9 promoter polymorphisms and acetylated c-Jun transcription factor for papillary thyroid carcinoma advancement Prediktivni značaj 2 polimorfizma u promotoru matriksne metaloproteinaze 9 i acetilovane forme c-Jun transkripcionog faktora u progresiji papilarnog tiroidnog karcinoma en ABSTRACT Papillary thyroid carcinoma represents a challenge from a prognostic standpoint. Molecular alterations responsible for PTC advancement include MMP-9 genetic promoter polymorphisms that bind transcription factors with varying degrees of affinity and, hence, constitute a predisposition for MMP-9 expression. We examined how two promoter polymorphisms (the -1562 C/T transition and -131 (CA)n tandem repeats) as well as levels of the c-Jun transcription factor and its modified form acetylated at Lys271 influence MMP-9 expression and PTC progression. A significant proportion of PTC samples were heterozygous for the (CA)n tandem repeat number, had a transcription-promoting T allele at -1562, and expressed high levels of c-Jun, acetylated c-Jun, and MMP-9 protein. The T allele at the -1562 position accompanied the elevated MMP-9 protein expression, while high acetylated c-Jun levels accompanied the high MMP-9 protein levels on mRNA. The -1562 C/T transition, MMP-9, and acetylated c-Jun were associated with the presence of extra-thyroid invasion and degree of tumor infiltration, while the T allele and acetylated c-Jun also correlated with tumor stage. We conclude that the -1562 MMP-9 polymorphism and levels of acetylated c-Jun affect PTC progression via modulation of MMP-9 levels. Genotyping the MMP-9 at -1562 and estimating the levels of MMP-9 and acetylated c-Jun in PTC may prove beneficial in identifying high-risk patients. papillary thyroid carcinoma, MMP-9, promoter polymorphism, transcription factors, carcinoma progression 1552099 10.3390/diagnostics12081953 2022-08-26T12:43:35.799Z 44 yes 46 Jelena Rončević University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia master biolog 0000-0003-3656-6420 Ilona Djorić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka person 0000-0001-5322-4559 Sonja Šelemetjev University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka person 0000-0002-2898-6671 Vladan Živaljević University of Belgrade, Faculty of Medicine, Serbia person Vesna Božić Clinical Center of Serbia, Department of Endocrine and Cardiovascular Pathology, Belgrade, Serbia person Tijana Išić Denčić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka person 0000-0001-8475-2266 Jelena Janković Miljuš University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0002-2589-3306 application/pdf 1995251 https://phaidrabg.bg.ac.rs/o:26354 no yes 16 70 92000001 11A29 11A2902 11A32 Diagnostics 12 8 MDPI 2022