Knockdown of α-Enolase (ENO1) to Suppress Glycolytic Pathway in Human Hepatocellular Carcinoma Cell Line (HepG2)
DOI:
https://doi.org/10.31351/vol33iss2pp156-160Abstract
ABSTRACT
Hepatocellular carcinoma therapies which are potentially curative depend on early diagnosis, but unfortunately only 20% is the 5-year survival rate of liver cancer despite of various treatment methods which progress continuously. Patients with hepatocellular carcinoma presenting with late stage disease despite established screening guidelines for patients at risk because of asymptomatic nature of this disease so finding effective treatments are imperative. Alpha-enolase has been noticed to be commonly over-expressed in tumors including hepatocellular carcinoma, it is one of the leading regulators of the Warburg effect, so plays an important role in carcinogenesis and tumor maintenance. In this study the cell line α-enolase short interference RNA was successfully constructed. In the α-enolase short interference RNA cell lines, messenger RNA and protein expression of α-enolase were lower than those in negative control and blank control groups. The pyruvate level was significantly inhibited, the proliferation ability was significantly suppressed. Our data provide strong evidence that α-enolase short interference RNA can efficiently suppress glycolysis pathway and thus the proliferation of Hep G2, which may provide a novel gene therapy for hepatocellular carcinoma.
Received 16/3/2023
Accepted 3/7/2023
Published 27/6/2024
References
Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017; 16(1): 1-8.
Wuestefeld A, Iakovleva V, Ling Yap SX, Leng Ong AB, Huang DQ, Ho Shuen TW et al. A Pro-Regenerative Environment Triggers Premalignant to Malignant Transformation of Senescent Hepatocytes. Cancer Res. 2023; 83: 428–40.
Chow AK, Yau SW, Ng L. Novel molecular targets in hepatocellular carcinoma. World J Clin Oncol. 2020 Aug 24;11(8):589-605.
Huang CK, Sun Y, Lv L, and Ping Y. ENO1 and Cancer. Mol Ther: Oncolytics. 2022; 24: 288-298.
Warburg O. On the origin of cancer cells. Science. 1956; 123: 309 314.
Altenberg B and Greulich KO. Genes of glycolysis are ubiq¬uitously overexpressed in 24 cancer classes. Genomics. 2004; 84: 1014 1020.
Kamani M, Akgor U, Gültekin M. Review of the literature on combined oral contraceptives and cancer. Ecancer. 2022; 16: 1-24.
Rio DC, Ares M, Hannon GJ, Nilsen TW. Purification of RNA using TRIzol (TRI reagent). Cold Spring Harbor Protocols. 2010; 2010(6): pdb-rot5439.
Barbas CF, Burton DR, Scott JK, Silverman GJ. Quantitation of DNA and RNA. Cold Spring Harbor Protocols. 2007; 2007(11): pdb-ip47.
Bachman J. Reverse-transcription PCR (rt-PCR). Methods in enzymology. 2013; 530: 67-74.
Zhang M, Yin Y, Dorfman RG, Zou T, Pan Y, Li Y et al. Down-regulation of HDAC3 inhibits growth of cholangiocarcinoma by inducing apoptosis. Oncotarget. 2017; 8(59): 99402.
Chamchoy K, Pakotiprapha D, Pumirat P, Leartsakulpanich U. Application of WST-8 based colorimetric NAD(P)H detection for quantitative dehydrogenase assays. BMC Biochemistry. 2019; 20(4): 1-14.
Sarı C, Kolaylı S and Eyüpoğlu FC. A Comparative Study of MTT and WST-1 Assays in Cytotoxicity Analysis. Haydarpasa Numune Med J. 2021; 61(3): 281–288.
Chen JM, Chiu S, Chen K, Huang YJ, Liao YA, Ricky Yu C. Enolase 1 differentially contributes to cell transformation in lung cancer but not in esophageal cancer. Oncol Lett. 2020; 19: 3189-3196.
Schofield L, Lincz LF, Skelding KA. Unlikely role of glycolytic enzyme α-enolase in cancer metastasis and its potential as a prognostic biomarker. Cancer Metastasis Treat. 2020; 6(10): 1-12.
Didiasova M, Schaefer L, Wygrecka M. When Place Matters: Shuttling of Enolase-1 Across Cellular Compartments. Front Cell Dev Biol. 2019; 7: 1-11.
Almaguel FA, Sanchez TW, Ortiz-Hernandez GL, Casiano CA. Alpha-Enolase: Emerging Tumor-Associated Antigen, Cancer Biomarker, and Oncotherapeutic Target. Front Genet. 2021; 11: 1-9.
Feng J, Li J, Wu L, Yu Q, Ji J, Wu J et al. Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2020; 39: 1-19.
Qiao H, Wang Y, Yuan W, Zhu B, Jiang L, Guan Q. Silencing of ENO1 by shRNA Inhibits the Proliferation of Gastric Cancer Cells. Technol Cancer Res Treat. 2018; 17: 1-9.
Song Y, Luo Q, Long H, Hu Z, Que T, Zhang X et al. Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma. Mol Cancer. 2014; 13: 1-12.
Qiao H, Wang Y-F, Yuan W-Z, Zhu B-D, Jiang L, Guan Q-L. Silencing of ENO1 by shRNA Inhibits the Proliferation of Gastric Cancer Cells. Technol Cancer Res Treatment. 2018; 17: 1-9.
H.-Y. ZANG, L.-G. GONG, S.-Y. LI, J.-G. HAO. Inhibition of α-enolase affects the biological activity of breast cancer cells by attenuating PI3K/Akt signaling pathway. Eur Rev Med Pharmacol Sci. 2020; 24: 249-257.
Li H, Ke F, Lin C, Lu M, Kuo Y, Wang Y et al. ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling–Driven Epithelial-to-Mesenchymal Transition. Cancer Res. 2021; 81: 4094–109.
Yang T, Shu X, Zhang H-W, Sun L-X, Yu L, Liu J et al. Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis. Cell Death Dis. 2020; 11: 1-13.
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