circ_0008043通过miR-198/SLC2A1轴促进肝癌糖酵解及肝癌发展

doi:10.11904/j.issn.1002-3070.2024.06.007

实用肿瘤学杂志 ›› 2024, Vol. 38 ›› Issue (6): 388-401.doi: 10.11904/j.issn.1002-3070.2024.06.007

circ_0008043通过miR-198/SLC2A1轴促进肝癌糖酵解及肝癌发展

张康军, 方泰石, 岑福兰, 闫旭, 陈琦军, 马楠

深圳市第三人民医院肝脏外科(肝移植)(南方科技大学第二附属医院)(深圳 518000)

收稿日期:2024-04-11 修回日期:2024-10-23 出版日期:2024-12-28 发布日期:2025-01-06
通讯作者: 张康军,E-mail:zkangjunhk@126.com
作者简介:张康军,男,(1986-),博士,主治医师,从事肝癌发生、发展机制、肝移植、再生医学、纳米医学的研究。
基金资助:
深圳市高水平医院建设专项经费(编号:XKJS-PWK-001);广东省医学科学技术研究基金(编号:B2023229);深圳市医学重点学科建设经费(编号:SZXK079);深圳市第三人民医院院内课题(编号:G2021003);深圳市基础研究资助项目(编号:JCYJ20210324131809027)

circ_0008043 promotes glycolysis of hepatocellular carcinoma and the development of hepatocellular carcinoma through miR-198/SLC2A1 axis

ZHANG Kangjun, FANG Taishi, CEN Fulan, YAN Xu, CHEN Qijun, MA Nan

Department of Liver Surgery(Liver Transplantation),The Third People's Hospital of Shenzhen(The Second Affiliated Hospital of Southern University of Science and Technology),Shenzhen 518000,China

Received:2024-04-11 Revised:2024-10-23 Online:2024-12-28 Published:2025-01-06

摘要/Abstract

摘要： 目的探究circ_0008043调控肝癌细胞糖酵解的机制。方法采用qPCR检测临床样本和肝癌细胞系中circ_0008043、miR-198和SLC2A1的表达,并用双荧光素酶报告实验验证circ_0008043与miR-198及miR-198与SLC2A1的靶向结合;通过向肝癌细胞系转染sh-circ_0008043/sh-NC、miR-198 inhibitor/miR-198 inhibitor-NC、miR-198 mimic/mimic NC或pcDNA3.1-SLC2A1/pcDNA3.1-NC检测circ_0008043、miR-198和SLC2A1对肝癌细胞糖酵解的影响;通过裸鼠移植瘤模型验证circ_0008043对肝癌肿瘤生长的影响。结果 circ_0008043在肝癌组织与细胞系中均高表达(P＜0.01),沉默circ_0008043可抑制肝癌细胞糖酵解;miR-198在肝癌组织与细胞系中表达降低(P＜0.001)且与circ_0008043表达呈负相关(r=-0.550,P＜0.001),沉默circ_0008043对糖酵解造成的抑制可通过抑制miR-198的表达被部分恢复;SLC2A1在肝癌组织与肝癌细胞系中表达水平高(P＜0.001),过表达SLC2A1可逆转由过表达miR-198对肝癌细胞糖酵解产生的抑制作用。裸鼠移植瘤实验表明,沉默circ_0008043可抑制肝癌肿瘤的生长(P＜0.001)。结论 circ_0008043通过miR-198/SLC2A1轴促进肝癌细胞糖酵解及肝癌的生长。

关键词: 肝癌, 糖酵解, circ_0008043, miR-198, SLC2A1

Abstract: Objective The aim of this study was to investigate the mechanism of circ_0008043 regulating glycolysis of hepatocellular carcinoma(HCC)cells. Methods The expression of circ_0008043,miR-198 and SLC2A1 in clinical samples and HCC cell lines was detected by qPCR,and the targeted binding of circ_0008043 to miR-198 and miR-198 to SLC2A1 was verified by dual luciferase reporting assay.HCC cells were transfected with sh-circ_0008043/sh-NC,miR-198 inhibitor/miR-198 inhibitor-NC,miR-198 mimic/mimic NC,or pcDNA3.1-SLC2A1/pcDNA3.1-NC to detected the effects of circ_0008043,miR-198 and SLC2A1 on the glycolysis of HCC cells.The effect of circ_0008043 on tumor growth in HCC was verified by HCC cell xenografts through a nude mouse model. Results circ_0008043 was highly expressed in both HCC tissues and cell lines(P＜0.01).Silencing circ_0008043 could inhibit the glycolysis of HCC cells.The expression of miR-198 was decreased in HCC tissues and cell lines(P＜0.001)and negatively correlated with the expression of circ_0008043(r=-0.550,P＜0.001).The inhibition of glycolysis caused by silencing circ_0008043 was partially restored by inhibiting miR-198 expression.SLC2A1 was highly expressed in HCC tissues and cell lines(P＜0.001),and overexpression of SLC2A1 reversed the inhibitory effect of miR-198 on glycolysis in HCC cells.The nude mouse experiment showed that silencing circ_0008043 could inhibit the growth of HCC cell xenografts(P＜0.001). Conclusion circ_0008043 promotes HCC cell glycolysis and growth through the miR-198/SLC2A1 axis.

Key words: Hepatocellular carcinoma, Glycolysis, circ_0008043, miR-198, SLC2A1

中图分类号:

R735.7

张康军, 方泰石, 岑福兰, 闫旭, 陈琦军, 马楠. circ_0008043通过miR-198/SLC2A1轴促进肝癌糖酵解及肝癌发展[J]. 实用肿瘤学杂志, 2024, 38(6): 388-401.

ZHANG Kangjun, FANG Taishi, CEN Fulan, YAN Xu, CHEN Qijun, MA Nan. circ_0008043 promotes glycolysis of hepatocellular carcinoma and the development of hepatocellular carcinoma through miR-198/SLC2A1 axis[J]. Journal of Practical Oncology, 2024, 38(6): 388-401.

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circ_0008043通过miR-198/SLC2A1轴促进肝癌糖酵解及肝癌发展

circ_0008043 promotes glycolysis of hepatocellular carcinoma and the development of hepatocellular carcinoma through miR-198/SLC2A1 axis

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