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成纤维细胞生长因子受体样-1:直肠腺癌的新治疗靶点和不良预后指标。

Fibroblast growth factor receptor-like-1: a new therapeutic target and unfavorable prognostic indicator for rectal adenocarcinoma.

机构信息

Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.

Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.

出版信息

J Recept Signal Transduct Res. 2020 Jun;40(3):257-263. doi: 10.1080/10799893.2020.1731534. Epub 2020 Feb 26.

DOI:10.1080/10799893.2020.1731534
PMID:32098557
Abstract

Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma activating the MAPK signaling pathway.

摘要

成纤维细胞生长因子受体样 1(FGFRL1)对于细胞迁移很重要,并与多种类型癌症的致瘤潜能相关。为了研究 FGFRL1 在直肠腺癌中的生物学功能和潜在机制,我们进行了这项研究。我们使用 TCGA 和 Oncomine 数据库分析了直肠腺癌患者中 FGFRL1 的表达及其与临床特征或总生存期(OS)的关系。采用 siRNA 策略敲低直肠腺癌细胞中的 FGFRL1 表达。通过 CCK8、集落形成、划痕愈合和 Transwell 实验检测细胞行为。通过 qRT-PCR 和 Western blot 鉴定 mRNA 和蛋白表达水平。FGFRL1 在直肠腺癌组织样本中,无论是结肠还是直肠,均显著上调。FGFRL1 的高表达诱导直肠腺癌患者预后较差。下调 FGFRL1 抑制 SW837 细胞的增殖、集落形成、迁移和侵袭。转染 si-FGFRL1 后,MAPK 通路相关蛋白 MEK 和 ERK 的磷酸化也降低。这些发现表明,FGFRL1 作为一种潜在的诱导剂,可能通过激活 MAPK 信号通路促进直肠腺癌的进展。

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