Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18.
Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18.
复制标题
HUR下调通过白介素18抑制食道癌的进展。
DOI：
10.4143/crt.2017.013
复制
发表时间：
2018-01
影响因子：
4.6
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Xu X;Song C;Chen Z;Yu C;Wang Y;Tang Y;Luo J
本研究旨在探讨人类抗原R（HuR）下调对食管鳞癌（ESCC）发生发展的影响及其可能的靶基因。在这项研究中，使用蛋白质组学测定来检测HuR下调后蛋白质的表达，并使用荧光素酶测定来检测白细胞介素18（IL-18）的3 '-非翻译区（3'-UTR）上HuR结合位点的潜在存在。此外，还采用集落形成试验、MTT、EdU掺入试验、Western blot、流式细胞术、免疫组织化学、transwell侵袭试验和伤口愈合试验。在本研究中，我们发现HuR蛋白和mRNA水平在肿瘤组织中的表达均高于癌旁组织。HuR下调显著抑制细胞增殖。此外，HuR基因敲低后，食管癌细胞的转移受到抑制，E-cadherin的表达增加，基质金属蛋白酶（MMP）2、MMP 9和vimentin的表达减少。此外，沉默HuR主要通过诱导G1期阻滞来干扰ESCC细胞的细胞周期。此外，蛋白质组学分析显示，TE-1细胞中HuR的下调导致100个上调和122个下调的蛋白质，包括IL-18作为显著上调的蛋白质。IL-18的表达受HuR的负调控。IL-18在食管鳞癌组织中的表达降低，外源性IL-18能显著抑制食管鳞癌细胞的增殖和转移。IL-18的3 '-UTR具有HuR结合位点，如体外荧光素酶测定所示。HuR通过靶向IL-18在食管癌的发生、发展中发挥重要作用，有望成为食管癌治疗的新靶点。
The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC). In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3’-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used. In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay. HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.
登录
查看更多内容
影响因子：
--
作者：
Ott CA;Linck L;Kremmer E;Meister G;Bosserhoff AK
通讯作者：
Bosserhoff AK
影响因子：
4.6
作者：
Ge J;Chang N;Zhao Z;Tian L;Duan X;Yang L;Li L
通讯作者：
Li L
影响因子：
4.7
作者：
Danilin, Sabrina;Sourbier, Carole;Massfelder, Thierry
通讯作者：
Massfelder, Thierry
影响因子：
10.2
作者：
Muralidharan R;Babu A;Amreddy N;Basalingappa K;Mehta M;Chen A;Zhao YD;Kompella UB;Munshi A;Ramesh R
通讯作者：
Ramesh R
影响因子：
30.8
作者：
Wu, Chen;Kraft, Peter;Lin, Dongxin
通讯作者：
Lin, Dongxin