Transcription Factor FOSL1 Promotes Angiogenesis of Colon Carcinoma by Regulating the VEGF Pathway Through Activating TIMP1

作者全名："Wang, Meng; Wang, Xian; Zhang, Yuanchuan; Gu, Jianhui; Zhang, Jie; Wen, Xing"

作者地址："[Wang, Meng; Zhang, Yuanchuan; Gu, Jianhui; Zhang, Jie; Wen, Xing] Chongqing Med Univ, Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Ctr Gastrointestinal & Minimally Invas Surg,Dept G, 19 Yangshi St, Chengdu 610031, Sichuan, Peoples R China; [Wang, Meng; Zhang, Yuanchuan; Gu, Jianhui; Zhang, Jie; Wen, Xing] Chongqing Med Univ, Affiliated Hosp Chengdu 2, 19 Yangshi St, Chengdu 610031, Sichuan, Peoples R China; [Wang, Xian] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Dept Anorectal, Affiliated Hosp, Chengdu 610031, Sichuan, Peoples R China; [Wang, Xian] Chongqing Med Univ, Affiliated Hosp Chengdu 2, Chengdu 610031, Sichuan, Peoples R China"

通信作者："Wen, X (通讯作者)，Chongqing Med Univ, Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Ctr Gastrointestinal & Minimally Invas Surg,Dept G, 19 Yangshi St, Chengdu 610031, Sichuan, Peoples R China.; Wen, X (通讯作者)，Chongqing Med Univ, Affiliated Hosp Chengdu 2, 19 Yangshi St, Chengdu 610031, Sichuan, Peoples R China."

来源：BIOCHEMICAL GENETICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001130114800003

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：TIMP1; FOSL1; Colon carcinoma; VEGF signaling pathway; Angiogenesis

摘要："Angiogenesis is the critical media for tumor growth and migration. Tissue Inhibitor Matrix Metalloproteinase-1 (TIMP1) acts as an oncogene in colon carcinoma (CC), but the biological effects of TIMP1 on angiogenesis remain an open issue. This study sought to explore the exact function and mechanism of TIMP1 in the angiogenesis of CC. Bioinformatics methods were utilized to analyze the expression of TIMP1 and its upstream transcription factor FOS-like antigen 1 (FOSL1) in the tumor tissue of CC. Meanwhile, in CC cell lines, real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot were utilized to verify the expression of TIMP1 and FOSL1. Cell counting kit-8 and tube formation assays were utilized to analyze the proliferation and angiogenesis abilities of human umbilical vein endothelial cells (HUVECs). Western blot was used to detect the protein expression of VEGFA, VEGFR-2, and VEGFR-3. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried out to explore the specific interaction between FOSL1 and TIMP1. The present study discovered that TIMP1 and FOSL1 were evidently up-regulated in CC tissue and cells. Meanwhile, TIMP1 was found to participate in regulating the signaling pathway of vascular endothelial growth factor (VEGF). Silenced TIMP1 conspicuously suppressed the proliferation and angiogenesis of HUVECs and reduced the protein expression of VEGFA, VEGFR-2, and VEGFR-3. Moreover, FOSL1 could promote TIMP1 transcription by binding with its promoter and the inhibition of TIMP1 expression obviously reversed the promotion effects of FOSL1 overexpression on the proliferation and angiogenesis of HUVECs. FOSL1 activated VEGF pathway by up-regulating TIMP1 expression, thereby advancing CC angiogenesis. We provided theoretical basis that the FOSL1/TIMP1/VEGF pathway might be a novel option for anti-angiogenesis therapy of CC."

基金机构：The Science and Technology Project of The Health Planning Committee of Sichuan Province

基金资助正文：No Statement Available