Artemisinin Mediates the Aerobic Glycolysis of Clear Cell Renal Cell Carcinomas via Regulating ENO2

Yingbao WANG; Xiaoyun LI; Ying TAN; Meng YANG; Yunqiang SHI; Qinrong PING; Libing HU; Yang YANG; Chunhui WANG

doi:10.12259/j.issn.2095-610X.S20231102

Volume 44 Issue 11

Nov. 2023

Turn off MathJax

Article Contents

Article Navigation > Journal of Kunming Medical University > 2023 > 44(11): 9-15

Yingbao WANG, Xiaoyun LI, Ying TAN, Meng YANG, Yunqiang SHI, Qinrong PING, Libing HU, Yang YANG, Chunhui WANG. Artemisinin Mediates the Aerobic Glycolysis of Clear Cell Renal Cell Carcinomas via Regulating ENO2[J]. Journal of Kunming Medical University, 2023, 44(11): 9-15. doi: 10.12259/j.issn.2095-610X.S20231102

Citation:

Yingbao WANG, Xiaoyun LI, Ying TAN, Meng YANG, Yunqiang SHI, Qinrong PING, Libing HU, Yang YANG, Chunhui WANG. Artemisinin Mediates the Aerobic Glycolysis of Clear Cell Renal Cell Carcinomas via Regulating ENO2[J]. Journal of Kunming Medical University, 2023, 44(11): 9-15. doi: 10.12259/j.issn.2095-610X.S20231102

Citation:

Yingbao WANG, Xiaoyun LI, Ying TAN, Meng YANG, Yunqiang SHI, Qinrong PING, Libing HU, Yang YANG, Chunhui WANG. Artemisinin Mediates the Aerobic Glycolysis of Clear Cell Renal Cell Carcinomas via Regulating ENO2[J]. Journal of Kunming Medical University, 2023, 44(11): 9-15. doi: 10.12259/j.issn.2095-610X.S20231102

PDF( 921 KB)

Artemisinin Mediates the Aerobic Glycolysis of Clear Cell Renal Cell Carcinomas via Regulating ENO2

doi: 10.12259/j.issn.2095-610X.S20231102

1.
Dept. of Urology，Yan’an Hospitalof Kunming city，Kunming Yunnan 650051
2.
Dept. of Education，QingDao Eighth People's Hospital，Qingdao Shandong 266041
3.
Dept. of Anesthesiology，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2023-09-05
Available Online: 2023-11-04
Publish Date: 2023-11-30

Abstract

Abstract

Objective To investigate Artemisinin-affected cell proliferation and aerobic glycolysis on clear cell renal carcinomas（ccRCC） through regulating ENO2 and clarify the mechanism. Methods ccRCC cell lines OSRC2 and ACHN were exposed to 0, 10, 20, 30, and 40 μmol/L Artemisinin, OSRC2 and ACHN cells treated with 25 μmol/L Artemisinin or transfected with si-ENO2 at the same time. CCK-8 assay detected cell proliferation, glucose consumption, and lactate production were detected by glucose test kit and lactate test kit. The expressions of HK2, LDHA, and ENO2 were detected by Western blot, and ENO2 mRNA expression was detected by RT-qPCR. Results The survival rate of OSRC2 and ACHN cells were decreased with the increase of Artemisinin concentration and treatment time, the IC50 of OSRC2 cells was 25.47 μmol/L, and the IC₅₀ of ACHN was 26.31 μmol/L. ENO2 was upregulated in OSRC2 and ACHN cells（P < 0.01）, and Artemisinin diminished ENO2 expression in cancer cells（all P < 0.05）. Exposure to Artemisinin（25 μmol/L） or knocking down ENO2 significantly inhibited the survival of OSRC2 and ACHN cells（all P < 0.001）, glucose consumption（P < 0.05）, lactate production（all P < 0.05） and protein expression of HK2 and LDHA（all P < 0.05）. Compared with si-ENO2 group, the survival rate（P < 0.001）, glucose consumption（P < 0.05）, lactate production（all P < 0.05） and the expression of HK2 and LDHA（all P < 0.05） of OSRC2 and ACHN cells in knocking down ENO2 and treated with 25 μmol/L Artemisinin group were decreased. Conclusion Artemisinin can inhibit the survival rate and aerobic glycolysis of ccRCC cells, and plays a role by downregulating the expression of ENO2 in ccRCC.
- Clear cells renal cell carcinomas,
- Aerobic glycolysis,
- Artemisinin,
- ENO2,
- Survival rate

FullText(HTML)

References(24)

References

[1]	Znaor A,Lortet-Tieulent J,Laversanne M,et al. International variations and trends in renal cell carcinoma incidence and mortality[J]. Eur Urol,2015,67(3):519-530. doi: 10.1016/j.eururo.2014.10.002
[2]	Baldewijns M M,Van Vlodrop I J,Schouten L J,et al. Genetics and epigenetics of renal cell cancer[J]. Biochim Biophys Acta,2008,1785(2):133-155.
[3]	Vaupel P,Schmidberger H,Mayer A. The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression[J]. Int J Radiat Biol,2019,95(7):912-919. doi: 10.1080/09553002.2019.1589653
[4]	Nocera G,Jacob C. Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury[J]. Cell Mol Life Sci,2020,77(20):3977-3989. doi: 10.1007/s00018-020-03516-9
[5]	Reed G H,Poyner R R,Larsen T M,et al. Structural and mechanistic studies of enolase[J]. Curr Opin Struct Biol,1996,6(6):736-743. doi: 10.1016/S0959-440X(96)80002-9
[6]	Chen W J,Yang W,Gong M,et al. ENO2 affects the EMT process of renal cell carcinoma and participates in the regulation of the immune microenvironment[J]. Oncol Rep,2023,49(2):33.
[7]	Tang C,Wang M,Dai Y,et al. Krüppel-like factor 12 suppresses bladder cancer growth through transcriptionally inhibition of enolase 2[J]. Gene,2021,769:145338.
[8]	Fang L,Ye T,An Y. Circular RNA FOXP1 induced by ZNF263 upregulates U2AF2 expression to accelerate renal cell carcinoma tumorigenesis and warburg effect through sponging miR-423-5p[J]. J Immunol Res,2021,2021:8050993.
[9]	Wang M,Chen H,He X,et al. Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels[J]. J Gastrointest Oncol,2022,13(5):2144-2153. doi: 10.21037/jgo-22-877
[10]	Farhan M,Silva M,Xingan X,et al. Artemisinin inhibits the migration and invasion in uveal melanoma via inhibition of the PI3K/AKT/mTOR signaling pathway[J]. Oxid Med Cell Longev,2021,2021:9911537.
[11]	Wang Z,Li M,Liu Y,et al. Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response-induced upregulation of CHAC1 expression[J]. Oncol Rep,2021,46(5):240. doi: 10.3892/or.2021.8191
[12]	Cai X,Miao J,Sun R,et al. Dihydroartemisinin overcomes the resistance to osimertinib in EGFR-mutant non-small-cell lung cancer[J]. Pharmacol Res,2021,170:105701.
[13]	Yu C,Sun P,Zhou Y,et al. Inhibition of AKT enhances the anti-cancer effects of Artemisinin in clear cell renal cell carcinoma[J]. Biomed Pharmacother,2019,118:109383.
[14]	Zhang M X,Wang J L,Mo C Q,et al. CircME1 promotes aerobic glycolysis and sunitinib resistance of clear cell renal cell carcinoma through cis-regulation of ME1[J]. Oncogene,2022,41(33):3979-3990. doi: 10.1038/s41388-022-02386-8
[15]	He Y,Wang X,Lu W,et al. PGK1 contributes to tumorigenesis and sorafenib resistance of renal clear cell carcinoma via activating CXCR4/ERK signaling pathway and accelerating glycolysis[J]. Cell Death Dis,2022,13(2):118. doi: 10.1038/s41419-022-04576-4
[16]	Li J,Zhang S,Liao D,et al. Overexpression of PFKFB3 promotes cell glycolysis and proliferation in renal cell carcinoma[J]. BMC Cancer,2022,22(1):83. doi: 10.1186/s12885-022-09183-2
[17]	Chen X,Li Z,Yong H,et al. Trim21-mediated HIF-1α degradation attenuates aerobic glycolysis to inhibit renal cancer tumorigenesis and metastasis[J]. Cancer Lett,2021,508:115-126. doi: 10.1016/j.canlet.2021.03.023
[18]	Gao L,Yang F,Tang D,et al. Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development[J]. J Exp Clin Cancer Res,2023,42(1):1. doi: 10.1186/s13046-022-02574-0
[19]	Liu D,Mao Y,Chen C,et al. Expression patterns and clinical significances of ENO2 in lung cancer: an analysis based on Oncomine database[J]. Ann Transl Med,2020,8(10):639. doi: 10.21037/atm-20-3354
[20]	Soh M A,Garrett S H,Somji S,et al. Arsenic,cadmium and neuron specific enolase (ENO2,γ-enolase) expression in breast cancer[J]. Cancer Cell Int,2011,11(1):41. doi: 10.1186/1475-2867-11-41
[21]	Huang J,Yang M,Liu Z,et al. PPFIA4 promotes colon cancer cell proliferation and migration by enhancing tumor glycolysis[J]. Front Oncol,2021,11:653200.
[22]	Peng J,Liu F,Zheng H,et al. IncRNA ZFAS1 contributes to the radioresistance of nasopharyngeal carcinoma cells by sponging hsa-miR-7-5p to upregulate ENO2[J]. Cell Cycle,2021,20(1):126-141. doi: 10.1080/15384101.2020.1864128
[23]	Liu C C,Wang H,Wang W D,et al. ENO2 promotes cell proliferation,glycolysis,and glucocorticoid-resistance in acute lymphoblastic leukemia[J]. Cell Physiol Biochem,2018,46(4):1525-1535. doi: 10.1159/000489196
[24]	Pan J,Jin Y,Xu X,et al. Integrated analysis of the role of enolase 2 in clear cell renal cell carcinoma[J]. Dis Markers,2022,2022:6539203.

Relative Articles(20)

Relative Articles

[1]	Hongsha PEI, Mingyang XU, Baoming JIA, Jianlong SU, Yigong FENG, Sibo XUE, Zhijun SONG. Correlation between Glycolytic Pathway of Monocytes and Intracranial Pressure and Clinical Prognosis in Patients with Hypertensive Cerebral Hemorrhage. Journal of Kunming Medical University, 2025, 46(5): 110-117. doi: 10.12259/j.issn.2095-610X.S20250513
[2]	Jingbo LIU, Yuan ZHANG, Mengjun LIU, Jing LIU, Hongli LIU, Jing ZHANG. Cyclin O Promotes the Proliferation and Metastasis of Cervical Cancer Cells by Regulating Glycolysis. Journal of Kunming Medical University, 2025, 46(7): 84-91. doi: 10.12259/j.issn.2095-610X.S20250710
[3]	Wenchao LI, Xue LI, Shanshan LIN, Yun MA, Guorui KANG, Ye CHEN. Effects of Sanqi Oral Liquid on Glycolysis，Renal Cell Apoptosis，and Keap1-Nrf2 Signaling Pathway in Diabetic Nephropathy Rats. Journal of Kunming Medical University, 2025, 46(12): 1-7.
[4]	Jiantong ZHANG, Zhenzhuang GAO, Zhixiu WANG, Lina SUN. Investigating the Effect of Dihydroartemisinin on Proliferation and Metastasis of Prostate Cancer Cells based on the SPOP/HnRNPK Pathway. Journal of Kunming Medical University, 2025, 46(11): 26-34. doi: 10.12259/j.issn.2095-610X.S20251104
[5]	Weixing ZENG, Yongwen HE. Research Progress on the Mechanisms of Action of Artemisinin and Its Derivatives in Cancer Therapy. Journal of Kunming Medical University, 2025, 46(4): 1-7. doi: 10.12259/j.issn.2095-610X.S20250401
[6]	Haijun WANG, Liangwu QIU, Yanbin XIYANG, Jundi PANG. Research Progress on Aerobic Exercise Intervention for Learning and Memory Ability in Chronic Cerebral Ischemia. Journal of Kunming Medical University, 2024, 45(3): 186-191. doi: 10.12259/j.issn.2095-610X.S20240328
[7]	Ting LI, Wei-Hua GUO. Research Progress of Glycolytic Reprogramming in Oral Squamous Cell Carcinoma. Journal of Kunming Medical University, 2023, 44(6): 155-161. doi: 10.12259/j.issn.2095-610X.S20230611
[8]	Yao ZOU, Ziyu WANG, Jiao LI, Xingxin LI, Yaqiong SHEN, Jing XU, Yan JIN. Association between LOXL2 and Snail Expression Levels and Overall Survival Rate after Surgery in Patients with Cholangiocarcinoma. Journal of Kunming Medical University, 2022, 43(12): 81-87. doi: 10.12259/j.issn.2095-610X.S20221215
[9]	Wei ZHANG, Baoquan WANG, Xifeng LEI, Xu WANG, Liang ZHANG. miR-125b-5p Regulates HK2 to Inhibit Proliferation and Glycolysis of Gallbladder Cancer Cells. Journal of Kunming Medical University, 2022, 43(12): 23-29. doi: 10.12259/j.issn.2095-610X.S20221206
[10]	Xiao-tao LI, Hai-feng WANG, Jian-song WANG. Advances on FBP1’s Role in Malignant Tumors. Journal of Kunming Medical University, 2021, 42(12): 156-160. doi: 10.12259/j.issn.2095-610X.S20211237
[11]	Jing YANG, Shu-xian WANG, Zhu ZHOU. Effect of Aerobic Exercise and Nutritional Management in Maintenance Hemodialysis Patients with Malnutrition. Journal of Kunming Medical University, 2020, 41(11): 68-71. doi: 10.12259/j.issn.2095-610X.S20201123
[12]	Li Si Wei , Wang Su Bin , Zhou Jiang Fan , Zhang Ming Qian , Gu Song Tao , Yang Ming Dong , Yang Rui , Yi Jing Shuai , Zhang Zhi Hua . . Journal of Kunming Medical University, 2018, 39(10): 7-12.
[13]	Zhao Yu , Zhao An Qi , Chen Chen , Wang Lin Lin . The Expression Changes of JNK3 and APP Protein in Apoptosis of Retinal Ganglion Cells after Optic Nerve Injury. Journal of Kunming Medical University, 2018, 39(02): 25-29.
[14]	Zhang He Yun , Zhong Yi Ming , Li Jian , Li Hui , Zheng Ying , Xiong Jie , Wang Ying Bao , Ping Qin Rong , Yang Yang . . Journal of Kunming Medical University, 2018, 39(12): 61-64.
[15]	Shen Zhi Xiang , Zhu Li Xun , Xu Wei Hong . 有氧运动对2型糖尿病大鼠AGE-RAGE轴及NF-κB通路的影响. Journal of Kunming Medical University, 2018, 39(01): 16-19.
[16]	Na Xin , Chen Li Jun , Luo Min , Chen Ya Juan , Qing Chen . . Journal of Kunming Medical University, 2017, 38(02): 33-37.
[17]	Liu Bin . . Journal of Kunming Medical University,
[18]	Tan Ying . . Journal of Kunming Medical University,
[19]	Gao Hong . . Journal of Kunming Medical University,
[20]	Li Xiong . . Journal of Kunming Medical University,