Yao Lv, Guo Xiaoqiang, Gui Yaoting
Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
Cell Physiol Biochem. 2018;45(3):984-992. doi: 10.1159/000487293. Epub 2018 Feb 8.
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.
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.
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.
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.
背景/目的:能量代谢重编程是许多癌症新出现的一个特征,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较少。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发生发展、细胞迁移和侵袭中的作用及机制。
采用定量实时PCR(qRT-PCR)检测ACSS2在癌组织和癌旁组织中的表达。通过RNA干扰抑制ACSS2表达,并通过qRT-PCR和蛋白质免疫印迹法进行验证。分别采用CCK8法和流式细胞术分析检测细胞增殖和凋亡情况。通过划痕试验和Transwell试验测定细胞迁移和侵袭能力。在敲低ACSS2表达后,通过qRT-PCR和蛋白质免疫印迹法检测自噬相关因子LAMP1的表达。
与癌旁组织相比,ACSS2在RCC癌组织中的表达上调,且与转移呈正相关。抑制ACSS2对RCC细胞增殖或凋亡无影响。然而,发现ACSS2表达降低可抑制RCC细胞迁移和侵袭。ACSS2被确定可促进LAMP1的表达,而LAMP1也可促进细胞迁移。该途径可能是ACSS2参与RCC发生发展的潜在机制。
这些数据表明,ACSS2是促进RCC发生发展的重要因素,对细胞迁移和侵袭至关重要,它通过增加LAMP1的表达来促进细胞迁移和侵袭。综上所述,这些发现揭示了RCC诊断和治疗的潜在靶点。