Rončević Jelena, Janković Miljuš Jelena, Išić Denčić Tijana, Božić Vesna, Živaljević Vladan, Šelemetjev Sonja, Đorić Ilona
Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia.
Department of Endocrine and Cardiovascular Pathology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.
Diagnostics (Basel). 2022 Aug 12;12(8):1953. doi: 10.3390/diagnostics12081953.
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.
从预后的角度来看，甲状腺乳头状癌是一个挑战。导致甲状腺乳头状癌进展的分子改变包括基质金属蛋白酶-9（MMP-9）基因启动子多态性，这些多态性以不同程度的亲和力结合转录因子，因此构成了MMP-9表达的易感性。我们研究了两种启动子多态性（-1562 C/T转换和-131 (CA)n串联重复）以及c-Jun转录因子及其在赖氨酸271处乙酰化的修饰形式的水平如何影响MMP-9的表达和甲状腺乳头状癌的进展。相当一部分甲状腺乳头状癌样本在(CA)n串联重复数上是杂合的，在-1562处有一个促进转录的T等位基因，并表达高水平的c-Jun、乙酰化c-Jun和MMP-9蛋白。-1562位置的T等位基因伴随着MMP-9蛋白表达的升高，而高乙酰化c-Jun水平伴随着mRNA上高MMP-9蛋白水平。-1562 C/T转换、MMP-9和乙酰化c-Jun与甲状腺外侵犯的存在和肿瘤浸润程度相关，而T等位基因和乙酰化c-Jun也与肿瘤分期相关。我们得出结论，-1562 MMP-9多态性和乙酰化c-Jun的水平通过调节MMP-9水平影响甲状腺乳头状癌的进展。对-1562处的MMP-9进行基因分型并估计甲状腺乳头状癌中MMP-9和乙酰化c-Jun的水平可能有助于识别高危患者。
