PYCR1:胰腺导管腺癌中的一种潜在预后生物标志物。

PYCR1: A Potential Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.

作者信息

Wang Huanyu, Mao Weilin, Lou Wenhui, Jin Dayong, Wu Wenchuan, Wang Dansong, Kuang Tiantao, Rong Yefei, Xu Xuefeng, Zhang Lei

机构信息

Department of General Surgery, Xuhui District Central Hospital, Shanghai, China.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

J Cancer. 2022 Feb 28;13(5):1501-1511. doi: 10.7150/jca.61498. eCollection 2022.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor with an extremely poor prognosis in digestive tumors. Pyrroline-5-carboxylate reductase 1 (PYCR1) plays an important role in tumor development. Therefore, we aimed to explore the effect of PYCR1 on the growth of PDAC cells. Tumor tissues and adjacent normal pancreatic tissues were collected from 89 patients with PDAC. And immunohistochemistry (IHC) was used to analyze the expression level of PYCR1 in both. RNA interference was used to inhibit the expression of PYCR1 in PANC- 1 and AsPC-1 cells. After infection, the expression of PYCR1 protein was detected by Western blot. The proliferation and growth of PDAC cells were detected by Celigo analysis, MTT, and clone formation assay. Cell apoptosis was analyzed by flow cytometry. Furthermore, the effect of PYCR1 interference on tumor growth was evaluated through injecting tumor cells subcutaneously into nude mice. The expression of PYCR1 in pancreatic cancer tissues was significantly higher than in paired adjacent normal pancreatic tissues (P <0.01). , the downregulation of PYCR1 expression significantly inhibited the cell proliferation and colony formation, and increased apoptosis in PANC-1 cells and AsPC-1 cells compared with the shCtrl group (P <0.01). And , PYCR1 interference also significantly inhibited tumor growth both in the tumor volume and weight. PYCR1 interference was able to inhibit cell proliferation and promote cell apoptosis of pancreatic cancer. The PYCR1 may serve as a potential therapeutic and prognostic biomarker for the treatment of pancreatic cancer.

摘要

胰腺导管腺癌(PDAC)是一种侵袭性很强的恶性肿瘤,在消化系统肿瘤中预后极差。吡咯啉-5-羧酸还原酶1(PYCR1)在肿瘤发展中起重要作用。因此,我们旨在探讨PYCR1对PDAC细胞生长的影响。从89例PDAC患者中收集肿瘤组织和相邻的正常胰腺组织。采用免疫组织化学(IHC)分析两者中PYCR1的表达水平。利用RNA干扰抑制PANC-1和AsPC-1细胞中PYCR1的表达。感染后,通过蛋白质免疫印迹法检测PYCR1蛋白的表达。通过Celigo分析、MTT和克隆形成试验检测PDAC细胞的增殖和生长。通过流式细胞术分析细胞凋亡。此外,通过将肿瘤细胞皮下注射到裸鼠体内评估PYCR1干扰对肿瘤生长的影响。胰腺癌组织中PYCR1的表达明显高于配对的相邻正常胰腺组织(P<0.01)。与shCtrl组相比,PYCR1表达的下调显著抑制了PANC-1细胞和AsPC-1细胞的细胞增殖和集落形成,并增加了细胞凋亡(P<0.01)。并且,PYCR1干扰在肿瘤体积和重量方面也显著抑制了肿瘤生长。PYCR1干扰能够抑制胰腺癌的细胞增殖并促进细胞凋亡。PYCR1可能作为治疗胰腺癌的潜在治疗和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44bf/8965111/d8e8f59c882e/jcav13p1501g001.jpg

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