|Table of Contents|

The effect of circ_ 0000619 on the proliferation and glutamine metabolism of esophageal squamous cell carcinoma cells by regulating miR-595/GLS axis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 11
Page:
2014-2020
Research Field:
Publishing date:

Info

Title:
The effect of circ_ 0000619 on the proliferation and glutamine metabolism of esophageal squamous cell carcinoma cells by regulating miR-595/GLS axis
Author(s):
ZHOU Yuxin12WU Linken12LI Sen12CHEN Shihang12QIAN Cuijuan12YAO Jun12
1.Medical College,Taizhou University,Zhejiang Taizhou 318000,China;2.Institute of Tumor,Taizhou University,Zhejiang Taizhou 318000,China.
Keywords:
circ_0000619esophageal squamous cell carcinomamiR-595GLSglutamine metabolism
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2023.11.008
Abstract:
Objective:To investigate the effect and its possible mechanism of circ_0000619/miR-595/GLS axis on cell proliferation,migration,invasion and glutamine metabolism of human esophageal squamous cell carcinoma (ESCC) KYSE150 cells.Methods:qPCR was used to detect circ_0000619,miR-595 and glutaminase (GLS) mRNA expression levels in KYSE150 cells.Western blot was used to detect GLS protein levels in KYSE150 cells.Cell counting kit-8 (CCK-8)and Transwell assays were used to investigate KYSE150 cell proliferation,invasion and migration,respectively.Glutamine consumption,glutamate production and ATP production levels were detected by indicated assay kits.Bioinformatics analysis technology and dual luciferase reporter gene assay were used to analyze and detect the interaction among circ_0000619,miR-595 and GLS mRNA.Results:circ_0000619 was highly expressed in ESCC cell lines,and its parental gene DENND4A mRNA was highly expressed in esophageal cancer tissues (P<0.01).Knockdown of circ_0000619 significantly inhibited the cell proliferation,invasion and migration of KYSE150 cells (P<0.01),and significantly inhibited the glutamine consumption level,glutamate and ATP production level of KYSE150 cells (P<0.01).Knockdown of circ_0000619 significantly increased the expression of miR-595 (P<0.01) and inhibited the mRNA (P<0.01) and protein expression of GLS.Dual luciferase reporter gene assay demonstrated that circ_0000619 had targeted binding with miR-595,and miR-595 had targeted binding with GLS in KYSE150 cells(all P<0.01).Glutamine metabolism and cell proliferation,were significantly decreased by circ_0000619 knockdown in KYSE150 cells,and these effects were partly reversed by miR-595 inhibition or GLS over-expression.Conclusion:circ_ 0000619 can enhance glutamine metabolism and cell proliferation of ESCC cells through targeted regulation of miR-595/GLS axis,and may become a potential target for ESCC therapy.

References:

[1]SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J].CA Cancer J Clin,2021,71(3):209-249.
[2]WATERS JK,REZNIK SI.Update on management of squamous cell esophageal cancer[J].Curr Oncol Rep,2022,24(3):375-385.
[3]FENG Q,ZHANG H,YAO D,et al.Emerging role of non-coding RNAs in esophageal squamous cell carcinoma [J].Int J Mol Sci,2019,21(1):258.
[4]FANG X,SHRESTHA SM,REN LH,et al.Biological and clinical implications of metastasis-associated circular RNAs in oesophageal squamous cell carcinoma [J].FEBS Open Bio,2021,11(11):2870-2887.
[5]SHEN Y,SHAO Y,NIU C,et al.Systematic identification of circRNA-miRNA-mRNA regulatory network in esophageal squamous cell carcinoma [J].Front Genet,2021,12:580390.
[6]REINFELD BI,MADDEN MZ,WOLF MM,et al.Cell-programmed nutrient partitioning in the tumour microenvironment [J].Nature,2021,593(7858):282-288.
[7]LIANG Z,ZHAO B,HOU J,et al.CircRNA circ-OGDH (hsa_circ_0003340) acts as a ceRNA to regulate glutamine metabolism and esophageal squamous cell carcinoma progression by the miR-615-5p/PDX1 axis [J].Cancer Manag Res,2021,13:3041-3053.
[8]ZHOU X,LIU K,CUI J,et al.Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer [J].J Exp Clin Cancer Res,2021,40(1):124.
[9]TAO M,ZHENG M,XU Y,et al.CircRNAs and their regulatory roles in cancers [J].Mol Med,2021,27(1):94.
[10]HARPER KL,MOTTRAM TJ,WHITEHOUSE A.Insights into the evolving roles of circular RNAs in cancer [J].Cancers (Basel),2021,13(16):4180.
[11]LI J,SUN D,PU W,et al.Circular RNAs in cancer:Biogenesis,function,and clinical significance [J].Trends Cancer,2020,6(4):319-336.
[12]LI T,SHAO Y,FU L,et al.Plasma circular RNA profiling of patients with gastric cancer and their droplet digital RT-PCR detection [J].J Mol Med (Berl),2018,96(1):85-96.
[13]MASISI BK,EL ANSARI R,ALFARSI L,et al.The role of glutaminase in cancer [J].Histopathology,2020,76(4):498-508.
[14]YANG WH,QIU Y,STAMATATOS O,et al.Enhancing the efficacy of glutamine metabolism inhibitors in cancer therapy [J].Trends Cancer,2021,7(8):790-804.
[15]CHU J,NIU X,CHANG J,et al.Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma [J].Theranostics,2020,10(8):3488-3502.
[16]SUN N,LIANG Y,CHEN Y,et al.Glutamine affects T24 bladder cancer cell proliferation by activating STAT3 through ROS and glutaminolysis [J].Int J Mol Med,2019,44(6):2189-2200.
[17]CEN L,LIU R,LIU W,et al.Competing endogenous RNA networks in glioma [J].Front Genet,2021,12:675498.
[18]BAI Q,PAN Z,NABI G,et al.Emerging role of competing endogenous RNA and associated noncoding RNAs in thyroid cancer [J].Am J Cancer Res,2022,12(3):961-973.
[19]CAO J,ZHANG X,XU P,et al.Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway [J].J Exp Clin Cancer Res,2021,40(1):6.
[20]LI K,CAO J,ZHANG Z,et al.Circular RNA circGSK3B promotes cell proliferation,migration,and invasion by sponging miR-1265 and regulating CAB39 expression in hepatocellular carcinoma [J].Front Oncol,2020,10:598256.

Memo

Memo:
国家级大学生创新创业训练计划项目(编号:202210350057);浙江省自然科学基金(编号:LTGY23H200001);浙江省基础公益研究计划社会发展项目(编号:LGF22H160015);浙江省大学生科技创新活动计划暨新苗人才计划项目(编号:2021R436018);浙江省台州市科技计划项目(编号:21ywb74,22ywa59)
Last Update: 2023-04-28