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首页> 外文期刊>Therapeutic advances in endocrinology and metabolism. >Expression and methylation status of LAMA2 are associated with the invasiveness of nonfunctioning PitNET
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Expression and methylation status of LAMA2 are associated with the invasiveness of nonfunctioning PitNET

机译：LAMA2的表达和甲基化状态与无效PitNET的侵袭性相关

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The laminin subunit alpha 2 (LAMA2) gene encodes an alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). In the current study, we investigated the relationship between LAMA2 promoter methylation status and the invasiveness of clinically nonfunctioning pituitary adenomas (PitNETs). Specimens from patients with nonfunctioning PitNET were classified into three groups according to preoperative computed tomography (CT)/magnetic resonance imaging findings: a normal group (n = 6), non-invasive group (n = 11) and invasive group (n = 6). LAMA2 expression was assessed using quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting, and the methylation status of the LAMA2 promoter region was observed using sodium bisulfite sequencing. Furthermore, 5-aza-2-deoxycytidine was used to explore the relationship between decreased LAMA expression and methylation in PitNET cells. According to the RT-qPCR and western blotting results, LAMA2 expression was downregulated in invasive PitNET, while the methylation of the LAMA2 promoter was increased. Methylation of the LAMA2 promoter decreased the expression of LAMA2. Thus, changes in LAMA2 expression due to promoter methylation were inversely correlated with the invasiveness of PitNET and the protein functions as a tumor suppressor. In addition, overexpression and demethylation of LAMA2 suppressed the invasion of PitNET cells, partially by exerting effects on the PTEN-PI3K/AKT signaling pathway and matrix metalloproteinase-9 (MMP-9). Furthermore, a xenograft model was also generated, and LAMA2 overexpression significantly suppressed tumor growth in vivo. Thus, LAMA2 expression and methylation patterns might be used as biomarkers to predict the prognosis of patients with PitNET.
机译：层粘连蛋白亚基α2（LAMA2）基因编码一条α2链，该链构成层粘连蛋白2（merosin）和层粘连蛋白4（s-merosin）的亚基之一。在当前的研究中，我们调查了LAMA2启动子甲基化状态与临床上无功能的垂体腺瘤（PitNETs）侵袭性之间的关系。根据术前计算机断层扫描（CT）/磁共振成像的结果，将PitNET无法正常工作的患者的标本分为三组：正常组（n = 6），无创组（n = 11）和有创组（n = 6 ）。使用定量实时聚合酶链反应（RT-qPCR）和Western blotting评估LAMA2表达，并使用亚硫酸氢钠测序观察LAMA2启动子区域的甲基化状态。此外，使用5-氮杂-2-脱氧胞苷探索PitNET细胞中LAMA表达降低与甲基化之间的关系。根据RT-qPCR和Western blotting结果，在侵入性PitNET中LAMA2表达下调，而LAMA2启动子的甲基化增加。 LAMA2启动子的甲基化降低了LAMA2的表达。因此，由于启动子甲基化导致的LAMA2表达变化与PitNET的侵袭性呈负相关，并且该蛋白起着抑癌作用。此外，LAMA2的过表达和去甲基化抑制了PitNET细胞的入侵，部分是通过对PTEN-PI3K / AKT信号通路和基质金属蛋白酶9（MMP-9）产生影响。此外，还生成了异种移植模型，并且LAMA2过表达显着抑制了体内肿瘤的生长。因此，LAMA2表达和甲基化模式可以用作预测PitNET患者预后的生物标志物。

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