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S1P Lyase siRNA Dampens Malignancy of DLD‐1 Colorectal Cancer Cells
Lipids ( IF 1.9 ) Pub Date : 2020-09-24 , DOI: 10.1002/lipd.12282 Wajiha Farha Faqar-Uz-Zaman 1 , Katrin G Schmidt 1 , Dominique Thomas 2 , Josef M Pfeilschifter 1 , Heinfried H Radeke 1 , Anja Schwiebs 1
Lipids ( IF 1.9 ) Pub Date : 2020-09-24 , DOI: 10.1002/lipd.12282 Wajiha Farha Faqar-Uz-Zaman 1 , Katrin G Schmidt 1 , Dominique Thomas 2 , Josef M Pfeilschifter 1 , Heinfried H Radeke 1 , Anja Schwiebs 1
Affiliation
Sphingosine‐1‐phosphate lyase 1 (S1P lyase or SGPL1) is an essential sphingosine‐1‐phosphate‐degrading enzyme. Its manipulation favors onset and progression of colorectal cancer and others in vivo. Thus, SGPL1 is an important modulator of cancer initiation. However, in established cancer, the impact of retrospective SGPL1 modulation is elusive. Herein, we analyzed how SGPL1 siRNA affects malignancy of the human colorectal cancer cells DLD‐1 and found that in parallel to the reduction of SGPL1 expression levels, migration, invasion, and differentiation status changed. Diminished SGPL1 expression was accompanied with reduced cell migration and cell invasion in scratch assays and transwell assays, whereas metabolic activity and proliferation was not altered. Decreased migration was attended by increased cell–cell‐adhesion through upregulation of E‐cadherin and formation of cadherin‐actin complexes. Spreading cell islets showed lower vimentin abundance in border cells. Furthermore, SGPL1 siRNA treatment induced expression of epithelial cell differentiation markers, such as intestinal alkaline phosphatase and cytokeratin 20. Hence, interference with SGPL1 expression augmented a partial redifferentiation of colorectal cancer cells toward normal colon epithelial cells. Our investigation showed that SGPL1 siRNA influenced tumorigenic activity of established colorectal cancer cells. We therefore suggest SGPL1 as a target for lowering malignant potential of already existing cancer.
中文翻译:
S1P 裂解酶 siRNA 抑制 DLD-1 结直肠癌细胞的恶性
1-磷酸鞘氨醇裂解酶 1(S1P 裂解酶或 SGPL1)是一种必需的 1-磷酸鞘氨醇降解酶。它的操作有利于体内结直肠癌和其他癌症的发生和进展. 因此,SGPL1 是癌症发生的重要调节剂。然而,在已确定的癌症中,回顾性 SGPL1 调制的影响是难以捉摸的。在此,我们分析了 SGPL1 siRNA 如何影响人结直肠癌细胞 DLD-1 的恶性程度,发现与 SGPL1 表达水平降低同时,迁移、侵袭和分化状态发生了变化。在划痕试验和 transwell 试验中,SGPL1 表达的减少伴随着细胞迁移和细胞侵袭的减少,而代谢活性和增殖没有改变。通过上调 E-钙粘蛋白和形成钙粘蛋白-肌动蛋白复合物来增加细胞-细胞粘附,从而减少迁移。扩散的细胞胰岛在边界细胞中显示较低的波形蛋白丰度。此外,SGPL1 siRNA 处理诱导上皮细胞分化标志物的表达,例如肠碱性磷酸酶和细胞角蛋白 20。因此,干扰 SGPL1 表达会增强结肠直肠癌细胞向正常结肠上皮细胞的部分再分化。我们的研究表明,SGPL1 siRNA 影响已建立的结直肠癌细胞的致瘤活性。因此,我们建议将 SGPL1 作为降低现有癌症恶性潜能的靶点。
更新日期:2020-09-24
中文翻译:
S1P 裂解酶 siRNA 抑制 DLD-1 结直肠癌细胞的恶性
1-磷酸鞘氨醇裂解酶 1(S1P 裂解酶或 SGPL1)是一种必需的 1-磷酸鞘氨醇降解酶。它的操作有利于体内结直肠癌和其他癌症的发生和进展. 因此,SGPL1 是癌症发生的重要调节剂。然而,在已确定的癌症中,回顾性 SGPL1 调制的影响是难以捉摸的。在此,我们分析了 SGPL1 siRNA 如何影响人结直肠癌细胞 DLD-1 的恶性程度,发现与 SGPL1 表达水平降低同时,迁移、侵袭和分化状态发生了变化。在划痕试验和 transwell 试验中,SGPL1 表达的减少伴随着细胞迁移和细胞侵袭的减少,而代谢活性和增殖没有改变。通过上调 E-钙粘蛋白和形成钙粘蛋白-肌动蛋白复合物来增加细胞-细胞粘附,从而减少迁移。扩散的细胞胰岛在边界细胞中显示较低的波形蛋白丰度。此外,SGPL1 siRNA 处理诱导上皮细胞分化标志物的表达,例如肠碱性磷酸酶和细胞角蛋白 20。因此,干扰 SGPL1 表达会增强结肠直肠癌细胞向正常结肠上皮细胞的部分再分化。我们的研究表明,SGPL1 siRNA 影响已建立的结直肠癌细胞的致瘤活性。因此,我们建议将 SGPL1 作为降低现有癌症恶性潜能的靶点。