The SP1/SNHG16/GLUT1 axis promotes prostate cancer proliferation and invasion by regulating glucose metabolism

SP1/SNHG16/GLUT1轴通过调节葡萄糖代谢促进前列腺癌的增殖和侵袭。

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Abstract

INTRODUCTION: The SP1/SNHG16/GLUT1 axis is involved in diverse cancer-related processes. This study was designed to study the role of the SP1/SNHG16/GLUT1 axis in prostate cancer (PCa) via modulation of glucose metabolism. MATERIAL AND METHODS: The expression profile of SNHG16 in PCa tissues was obtained from the online public database GEPIA (http://gepia.cancer-pku.cn/). Human prostate cancer cell lines, PC-3 and DU-145, were used in this study. Real-time qPCR was employed to determine the mRNA expression levels of SNHG16 and GLUT1. To assess cellular proliferation, CCK-8 assays were performed. Cellular invasion was evaluated using Transwell assays, and glycolysis was monitored through glucose uptake, lactate production, and ATP generation measurements. RESULTS: Analysis of GEPIA2 data revealed upregulation of SNHG16 in PCa tissues and a positive association between GLUT1 (SLC2A1) and SP1/SNHG16 expression in the correlation study. Consistently, SPI and SNHG16 were either overexpressed or knocked down in PCa cells to reveal the role of the SP1/SNHG16/GLUT1 axis. The results demonstrated that PC-3 and DU145 cell proliferation was promoted by the overexpression of either SPI or SNHG16. On the other hand, PC-3 and DU145 cell proliferation was reduced upon knockdown of SP1 or SNHG16. A real-time qPCR study revealed that GLUT1 mRNA was upregulated by SP1/SNHG16 overexpression and downregulated by SP1/SNHG16 knockdown. In PCa cells, overexpression of SNHG16/SP1 resulted in enhanced utilization of glucose, lactose, and ATP production, whereas SNHG16/SP1 knockdown had the reverse effect. Lastly, Transwell assay results showed that overexpression of SNHG16/SP1 promoted, while knockdown of SNHG16/SP1 inhibited, the invasiveness of PC-3 and DU145 PCa cells. CONCLUSIONS: Collectively, the evidence indicates that the SP1/SNHG16/GLUT1 axis regulates proliferation of PCa cells via the glycolytic route and thus may act as a therapeutic target for PCa treatment.

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