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。

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

作者信息

Huang Hua, Zhang Wen

机构信息

Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China.

Department of General Practice, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China.

出版信息

Arch Med Sci. 2024 Jul 28;21(2):638-647. doi: 10.5114/aoms/191153. eCollection 2025.

DOI:10.5114/aoms/191153

PMID:40395899

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12087323/

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.

摘要

引言

SP1/SNHG16/GLUT1轴参与多种癌症相关过程。本研究旨在通过调节葡萄糖代谢来研究SP1/SNHG16/GLUT1轴在前列腺癌（PCa）中的作用。

材料与方法

从在线公共数据库GEPIA（http://gepia.cancer-pku.cn/）获取PCa组织中SNHG16的表达谱。本研究使用了人前列腺癌细胞系PC-3和DU-145。采用实时定量PCR（qPCR）来测定SNHG16和GLUT1的mRNA表达水平。为评估细胞增殖，进行了CCK-8检测。使用Transwell检测评估细胞侵袭，并通过葡萄糖摄取、乳酸产生和ATP生成测量来监测糖酵解。

结果

GEPIA2数据分析显示PCa组织中SNHG16上调，且在相关性研究中GLUT1（SLC2A1）与SP1/SNHG16表达呈正相关。同样地，在PCa细胞中过表达或敲低SPI和SNHG16以揭示SP1/SNHG16/GLUT1轴的作用。结果表明，SPI或SNHG16的过表达促进了PC-3和DU145细胞的增殖。另一方面，敲低SP1或SNHG16后，PC-3和DU145细胞的增殖减少。实时qPCR研究表明，SP1/SNHG16过表达使GLUT1 mRNA上调，而SP1/SNHG16敲低使其下调。在PCa细胞中，SNHG16/SP1的过表达导致葡萄糖、乳糖利用增加和ATP产生增强，而SNHG16/SP1敲低则产生相反的效果。最后，Transwell检测结果显示，SNHG16/SP1的过表达促进了PC-3和DU145前列腺癌细胞的侵袭，而SNHG16/SP1敲低则抑制了其侵袭。