Background

Protein arginine methyltransferase 1 (PRMT1) is the founding member of the PRMT family of proteins, whose members catalyze methylation of arginine residues in various proteins. Although several studies have reported upregulation of PRMT1 in various cancer types, the expression pattern and the underlying mechanism of PRMT1 action in pancreatic ductal adenocarcinoma (PDAC) are still unclear.

Methods

Immunohistochemistry staining as well as RT-PCR was used to determine the expression pattern of PRMT1 in clinical PDAC samples. Lentivirus packaging and transfection were employed to construct cell lines with PRMT1 overexpression or knockdown. MTT and crystal violet assays were used to determine the proliferation rates of PDAC cells. β-catenin transcription activity was measured using a TOPFlash assay. PRMT1 binding to the promoter region of CTNNB1 was determined by ChIP-qPCR assay.

Results

Elevated PRMT1 expression was found in PDAC tissue samples compared to noncancerous normal tissues in 41 patients using a real-time PCR assay and in 90 patients using a tissue microarray (TMA) in conjunction with immunohistochemistry. Analysis of the PRMT1 expression data and PDAC clinical features revealed that PRMT1 expression was significantly correlated with PDAC tumor size and prognosis in postoperative patients. Additional functional experiments revealed that PRMT1 expression promoted the growth of pancreatic cancer-derived cells, both in vitro and in vivo. Mechanistically, we found that PRMT1 increased the cellular β-catenin level. We also found that PRMT1 and β-catenin were co-expressed in TCGA and GTEx datasets containing 370 samples.

Conclusions

Collectively, our study provides novel insight into the expression and function of PRMT1 in PDAC and indicates that PRMT1 may serve as a therapeutic target for treating patients with pancreatic ductal adenocarcinoma.

中文翻译：

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PRMT1促进胰腺癌的生长，并预测不良预后。

背景

蛋白质精氨酸甲基转移酶1（PRMT1）是PRMT蛋白质家族的创始成员，其成员催化各种蛋白质中精氨酸残基的甲基化。尽管有几项研究报道了PRMT1在各种类型的癌症中的上调，但PRMT1在胰腺导管腺癌（PDAC）中的表达模式和作用的潜在机制仍不清楚。

方法

免疫组织化学染色以及RT-PCR用于确定PRMT1在临床PDAC样品中的表达模式。慢病毒包装和转染用于构建PRMT1过表达或敲低的细胞系。使用MTT和结晶紫测定法确定PDAC细胞的增殖速率。使用TOPFlash测定法测量β-catenin转录活性。通过ChIP-qPCR分析确定PRMT1与CTNNB1启动子区的结合。

结果

在41例患者中，使用实时PCR检测，在PDAC组织样本中与非癌性正常组织相比，PRMT1表达升高；在90例中，使用组织微阵列（TMA）结合免疫组织化学，发现PRMT1表达升高。对PRMT1表达数据和PDAC临床特征的分析表明，PRMT1表达与术后患者的PDAC肿瘤大小和预后显着相关。其他功能性实验显示PRMT1表达在体外和体内均可促进胰腺癌衍生细胞的生长。从机理上讲，我们发现PRMT1增加了细胞β-catenin的水平。我们还发现PRMT1和β-catenin在TCGA和GTEx数据集中共表达了370个样本。

结论

总体而言，我们的研究提供了PRMT1在PDAC中的表达和功能的新颖见解，并表明PRMT1可以作为治疗胰腺导管腺癌患者的治疗靶标。