LncRNA FENDRR in Carcinoma-Associated Fibroblasts Regulates the Angiogenesis of Oral Squamous Cell Carcinoma Through the PI3K/AKT Pathway.
LncRNA FENDRR in Carcinoma-Associated Fibroblasts Regulates the Angiogenesis of Oral Squamous Cell Carcinoma Through the PI3K/AKT Pathway.
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癌相关成纤维细胞中的 LncRNA FENDRR 通过 PI3K/AKT 途径调节口腔鳞状细胞癌的血管生成
DOI：
10.3389/fonc.2021.616576
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发表时间：
2021
影响因子：
4.7
通讯作者：
Shang Z
中科院分区：
文献类型：
--
作者：
Xu Y;Jiang E;Shao Z;Shang Z
血管生成对肿瘤的发展至关重要。研究表明，癌相关成纤维细胞（CAFs）参与调节肿瘤血管生成，但其机制尚不清楚。近年来，长链非编码rna （long noncoding rna, lncRNAs）已被证明在多种肿瘤的血管生成中发挥重要作用。然而，CAFs对lncRNAs介导的口腔鳞状细胞癌（OSCC）血管生成的调控作用目前尚无相关研究。通过分析微阵列数据，我们发现与正常组织相比，OSCC患者中lncRNA FOXF1邻近非编码发育调节RNA （FENDRR）的表达下调。定量聚合酶链反应（qPCR）结果显示，与OSCC患者的正常成纤维细胞（NFs）相比，CAFs中FENDRR的表达较低。KEGG通路分析显示，HNSCC患者CAFs和NFs之间的一些差异表达基因富集于PI3K/AKT通路。进一步实验证实，下调FENDRR可激活NFs中PI3K/AKT通路，增强基质金属蛋白酶9 （matrix metalloproteinase 9, MMP9）的表达。而过表达FENDRR则有相反的效果。此外，我们将人脐静脉内皮细胞（HUVECs）与CAFs共培养，HUVECs与过表达FENDRR的CAFs共培养后，其成管能力明显下降。然而，激活过表达FENDRR的CAFs的AKT通路可以减弱FENDRR对血管生成的抑制作用。综上所述，我们的实验首次关注了CAFs中lncRNAs对OSCC血管生成的影响，证明了FENDRR通过PI3K/AKT通路介导CAFs对OSCC血管生成的调控。
Angiogenesis is essential for the development of tumors. Studies have shown that carcinoma-associated fibroblasts (CAFs) are involved in regulating tumor angiogenesis, but the mechanism remains unclear. Recently, long noncoding RNAs (lncRNAs) have been proved to play an important role in the angiogenesis of various tumors. However, there is currently no research involving the regulation of CAFs on the angiogenesis of oral squamous cell carcinoma (OSCC) mediated by lncRNAs. By analyzing microarray data, we identified that the expression of lncRNA FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) in OSCC patients is downregulated, compared to that in normal tissues. Quantitative polymerase chain reaction (qPCR) results demonstrated that FENDRR expression is lower in CAFs compared to normal fibroblasts (NFs) of OSCC patients. KEGG pathway analysis revealed that some genes differentially expressed between CAFs and NFs of HNSCC patients are enriched to the PI3K/AKT pathway. Further experiments confirmed that the downregulation of FENDRR can activate the PI3K/AKT pathway in NFs and enhances the expression of matrix metalloproteinase 9 (MMP9). The overexpression of FENDRR had the opposite effect. Besides, we co-cultured human umbilical vein endothelial cells (HUVECs) with CAFs, and the tube-forming ability of HUVECs co-cultured with CAFs overexpressing FENDRR decreased significantly. However, activation of the AKT pathway of CAFs overexpressing FENDRR can weaken the inhibitory effect of FENDRR on angiogenesis. In summary, our experiments are focused on the influence of lncRNAs in CAFs on OSCC angiogenesis for the first time and prove that FENDRR mediates CAFs’ regulation of OSCC angiogenesis through the PI3K/AKT pathway.
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影响因子：
14.9
作者：
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DOI：
10.1186/s13046-018-0911-3
发表时间：
2018-10-03
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
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作者：
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通讯作者：
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