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The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms
Cancer Science ( IF 4.5 ) Pub Date : 2022-02-18 , DOI: 10.1111/cas.15301 Liping He 1, 2 , Steeve Boulant 3 , Megan Stanifer 3 , Cuncai Guo 3 , Anna Nießen 1 , Mingyi Chen 1, 4 , Klaus Felix 1 , Frank Bergmann 5 , Oliver Strobel 1 , Simon Schimmack 1
Cancer Science ( IF 4.5 ) Pub Date : 2022-02-18 , DOI: 10.1111/cas.15301 Liping He 1, 2 , Steeve Boulant 3 , Megan Stanifer 3 , Cuncai Guo 3 , Anna Nießen 1 , Mingyi Chen 1, 4 , Klaus Felix 1 , Frank Bergmann 5 , Oliver Strobel 1 , Simon Schimmack 1
Affiliation
MEN1, which encodes menin protein, is the most frequently mutated gene in pancreatic neuroendocrine neoplasms (pNEN). Pleiotrophin (PTN) has been reported as a downstream factor of menin that promotes metastasis in different tumor entities. In this study, the effect of menin and its link to PTN were assessed using features of pNEN cells and the outcome of patients with pNEN. The expression levels of menin and PTN in tissues from patients with pNEN were examined using qRT-PCR and western blot and compared with their metastasis status. Functional assays, including transwell migration/invasion and scratch wound-healing assays, were performed on specifically designed CRISPR/Cas9-mediated MEN1-knockout (MEN1-KO) pNEN cell lines (BON1MEN1-KO and QGP1MEN1-KO) to study the metastasis of pNEN. Among 30 patients with menin-negative pNEN, 21 revealed a strong protein expression of PTN. This combination was associated with metastasis and shorter disease-free survival. Accordingly, in BON1MEN1-KO and QGP1MEN1-KO cells, PTN protein expression was positively associated with enhanced cell migration and invasion, which could be reversed using PTN silencing. PTN is a predicting factor of metastatic behavior of menin-deficient-pNEN. In vitro, menin is able to both promote and suppress the metastasis of pNEN by regulating PTN expression depending on the tumoral origin of pNEN cells.
中文翻译:
Menin 和 pleiotrophin 在胰腺神经内分泌肿瘤的肿瘤生物学中的联系
MEN1编码 menin 蛋白,是胰腺神经内分泌肿瘤 (pNEN) 中最常发生突变的基因。Pleiotrophin (PTN) 已被报道为 menin 的下游因子,可促进不同肿瘤实体的转移。在这项研究中,使用 pNEN 细胞的特征和 pNEN 患者的结果评估了 menin 的作用及其与 PTN 的联系。使用 qRT-PCR 和蛋白质印迹检测 pNEN 患者组织中 menin 和 PTN 的表达水平,并与它们的转移状态进行比较。在专门设计的 CRISPR/Cas9 介导的MEN1敲除 (MEN1-KO) pNEN 细胞系(BON1 MEN1-KO和 QGP1 MEN1-KO) 研究 pNEN 的转移。在 30 例 menin 阴性 pNEN 患者中,21 例显示 PTN 蛋白强烈表达。这种组合与转移和更短的无病生存期有关。因此,在 BON1 MEN1-KO和 QGP1 MEN1-KO细胞中,PTN 蛋白表达与增强的细胞迁移和侵袭呈正相关,这可以通过 PTN 沉默来逆转。PTN是menin-deficient-pNEN转移行为的预测因素。在体外,menin 能够通过调节 PTN 的表达来促进和抑制 pNEN 的转移,这取决于 pNEN 细胞的肿瘤起源。
更新日期:2022-02-18
中文翻译:
Menin 和 pleiotrophin 在胰腺神经内分泌肿瘤的肿瘤生物学中的联系
MEN1编码 menin 蛋白,是胰腺神经内分泌肿瘤 (pNEN) 中最常发生突变的基因。Pleiotrophin (PTN) 已被报道为 menin 的下游因子,可促进不同肿瘤实体的转移。在这项研究中,使用 pNEN 细胞的特征和 pNEN 患者的结果评估了 menin 的作用及其与 PTN 的联系。使用 qRT-PCR 和蛋白质印迹检测 pNEN 患者组织中 menin 和 PTN 的表达水平,并与它们的转移状态进行比较。在专门设计的 CRISPR/Cas9 介导的MEN1敲除 (MEN1-KO) pNEN 细胞系(BON1 MEN1-KO和 QGP1 MEN1-KO) 研究 pNEN 的转移。在 30 例 menin 阴性 pNEN 患者中,21 例显示 PTN 蛋白强烈表达。这种组合与转移和更短的无病生存期有关。因此,在 BON1 MEN1-KO和 QGP1 MEN1-KO细胞中,PTN 蛋白表达与增强的细胞迁移和侵袭呈正相关,这可以通过 PTN 沉默来逆转。PTN是menin-deficient-pNEN转移行为的预测因素。在体外,menin 能够通过调节 PTN 的表达来促进和抑制 pNEN 的转移,这取决于 pNEN 细胞的肿瘤起源。