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Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

机译:乙酰辅酶A合成酶2通过上调溶酶体相关膜蛋白1的表达促进细胞迁移和侵袭肾细胞癌。

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Background/Aims Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC.
机译:背景/目的重新编程能量代谢是许多癌症的新兴特征,这种改变在肾细胞癌(RCC)中尤为明显。然而,关于脂质代谢的研究很少。本研究探讨了脂质代谢相关的乙酰辅酶A合成酶2(ACSS2)在RCC发育,细胞迁移和侵袭中的功能和机制。方法采用实时荧光定量PCR(qRT-PCR)检测ACSS2在癌组织及癌旁组织中的表达。通过RNA干扰实现了对ACSS2表达的抑制,这已通过qRT-PCR和Western blotting证实。通过CCK8测定和流式细胞术分析分别检测细胞增殖和凋亡。细胞的迁移和侵袭通过划痕和transwell测定来确定。敲低ACSS2表达后,通过qRT-PCR和Western印迹法检测自噬相关因子LAMP1的表达。结果与癌旁组织相比,RCS癌组织中ACSS2的表达上调,与转移密切相关。抑制ACSS2对RCC细胞增殖或凋亡没有影响。然而,发现降低的ACSS2表达抑制RCC细胞迁移和侵袭。确定ACSS2可以促进LAMP1的表达,这也可以促进细胞迁移。该途径可能被认为是ACSS2参与RCC发展的潜在机制。结论这些数据表明,ACSS2是促进RCC发育的重要因素,对于细胞迁移和侵袭至关重要,它通过增加LAMP1的表达而促进。综上所述,这些发现揭示了RCC诊断和治疗的潜在目标。

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