成纤维细胞生长因子受体样 1 在食管癌中的异常表达及其受 miR-107 的调控。
Aberrant Expression of FGFRL1 in Esophageal Cancer and Its Regulation by miR-107.
机构信息
University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, New Delhi, India.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
出版信息
Asian Pac J Cancer Prev. 2023 Apr 1;24(4):1331-1341. doi: 10.31557/APJCP.2023.24.4.1331.
BACKGROUND
Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of cancer. However, little is known about the expression and function of FGFRL1 in esophageal cancer (EC).
METHODS
We systematically evaluated the expression of FGFRL1 in TCGA and GETex datasets followed by expression analysis in EC cell lines and clinical specimens using immunofluorescence (IF) and immunohistochemistry (IHC) respectively.
RESULTS
GEPIA analysis on TCGA and GETex datasets identified significant upregulation of FGFRL1 in EC patients (n=182) compared to normal controls (n=286, p<0.05). IHC analysis showed significantly higher FGFRL1 expression in EC tissues as compared to the distant matched non-malignant tissues (p<0.001). Immunoflourescence in EC cells suggested increased expression of FGFRL1 from WDSCC (KYSE30) to MDSCC (KYSE140) and finally to PDSCC (KYSE410). In-silico tools predicted miR-107 as most significant miRNA regulating FGFRL1 expression. qRT-PCR revealed miR-107 expression to be significantly and inversely correlated with FGFRL1 expression in 73% (22/30) EC tissues (p=0.015) and over-expression of miR-107 resulted in significantly decreased expression of FGFRL1 at mRNA (fold change=0.11, p=0.0016) as well as protein level in miR-107 versus NC treated cells. Luciferase reporter assay using FGFRL1-3'UTR further confirmed it to be a direct target of miR-107.
CONCLUSION
Our results herein document clinical as well as functional relevance of FGFRL1 in EC and its regulation by miR-107.
背景
成纤维细胞生长因子受体是生长因子受体酪氨酸激酶，在胚胎发生、组织稳态和癌症发展中发挥作用。然而，关于成纤维细胞生长因子受体样 1（FGFRL1）在食管癌（EC）中的表达和功能知之甚少。
方法
我们系统地评估了 TCGA 和 GETex 数据集的 FGFRL1 表达情况，然后分别通过免疫荧光（IF）和免疫组织化学（IHC）分析在 EC 细胞系和临床标本中进行表达分析。
结果
TCGA 和 GETex 数据集的 GEPIA 分析表明，与正常对照（n=286）相比，EC 患者（n=182）中 FGFRL1 的表达显著上调（p<0.05）。IHC 分析显示，EC 组织中 FGFRL1 的表达明显高于远处匹配的非恶性组织（p<0.001）。EC 细胞中的免疫荧光显示，从 WDSCC（KYSE30）到 MDSCC（KYSE140），最后到 PDSCC（KYSE410），FGFRL1 的表达增加。计算机工具预测 miR-107 是调节 FGFRL1 表达的最重要的 miRNA。qRT-PCR 显示，在 73%（22/30）的 EC 组织中，miR-107 的表达与 FGFRL1 的表达呈显著负相关（p=0.015），并且 miR-107 的过表达导致 miR-107 处理细胞中 FGFRL1 的表达在 mRNA（倍数变化=0.11，p=0.0016）和蛋白水平均显著降低。使用 FGFRL1-3'UTR 的荧光素酶报告基因检测进一步证实它是 miR-107 的直接靶标。
结论
我们的研究结果记录了 FGFRL1 在 EC 中的临床和功能相关性及其受 miR-107 的调节。
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