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Current Bioinformatics


ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Bioinformatics Study of RNA Interference on the Effect of HIF-1α on Apelin Expression in Nasopharyngeal Carcinoma Cells

Author(s): Gang Xu, Xianming Li, Dong Yang, Shihai Wu, Dong Wu and Maosheng Yan*

Volume 14 , Issue 5 , 2019

Page: [386 - 390] Pages: 5

DOI: 10.2174/1574893614666190109155825

Price: $65


Background: HIF-1α can affect the apelin expression and participates in the developments in cancers but the mechanism need to be explored further.

Objective: This paper investigates apelin expression in nasopharyngeal carcinoma CNE-2 cells and its regulation by hypoxia inducible factor-1α (HIF-1α) under hypoxic conditions.

Methods: CoCl2 was used to induce hypoxia in CNE-2 cells for 12h, 24h and 48h. HIF-1α small interference RNA (siRNA) was transfected into CNE-2 cells using a transient transfection method. HIF-1α and apelin mRNA levels were detected by real time PCR. Western blot was used to measure HIF-1α protein expression. The concentration of apelin in cell culture supernatant was determined by enzyme linked immunosorbent assay (ELISA).

Results: HIF-1α and apelin mRNA levels and protein expression in CNE-2 cells increased gradually with increased duration of hypoxic exposure and were significantly reduced in HIF-1α siRNA transfected cells exposed to the same hypoxic conditions.

Conclusion: Apelin expression is induced by hypoxia and regulated by HIF-1α in CNE-2 cells.

Keywords: Nasopharyngeal carcinoma, hypoxia inducible factor-1 alpha, apelin, RNA interference, CNE-2, western blot.

Graphical Abstract
Muto J, Shirabe K, Yoshizumi T, et al. The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. Anticancer Res 2014; 34(10): 5313-20.
Tang CM, Yu J. Hypoxia-inducible factor-1 as a therapeutic target in cancer. J Gastroenterol Hepatol 2013; 28(3): 401-5.
He L, Xu J, Chen L, Li L. Apelin/APJ signaling in hypoxia-related diseases. Clin Chim Acta 2015; 451(Pt B): 191-8.
Sun X, Su S, Chen C, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol 2014; 110(3): 398-403.
Lee SH, Jeong D, Han YS, Baek MJ. Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis. Ann Surg Treat Res 2015; 89(1): 1-8.
Folino A, Montarolo PG, Samaja M, Rastaldo R. Effects of apelin on the cardiovascular system. Heart Fail Rev 2015; 20(4): 505-18.
Pitkin SL, Maguire JJ, Bonner TI, Davenport AP. International Union of Basic and Clinical Pharmacology. LXXIV. Apelin receptor nomenclature, distribution, pharmacology, and function. Pharmacol Rev 2010; 62(3): 331-42.
Cox CM, D’Agostino SL, Miller MK, Heimark RL, Krieg PA. Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo. Dev Biol 2006; 296(1): 177-89.
Kleinz MJ, Skepper JN, Davenport AP. Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells. Regul Pept 2005; 126(3): 233-40.
Masri B, Morin N, Cornu M, Knibiehler B, Audigier Y. Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells. FASEB J 2004; 18(15): 1909-11.
Kasai A, Shintani N, Oda M, et al. Apelin is a novel angiogenic factor in retinal endothelial cells. Biochem Biophys Res Commun 2004; 325(2): 395-400.
Kidoya H, Kunii N, Naito H, et al. The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy. Oncogene 2012; 31(27): 3254-64.
Sorli SC, Le Gonidec S, Knibiehler B, Audigier Y. Apelin is a potent activator of tumour neoangiogenesis. Oncogene 2007; 26(55): 7692-9.
Lacquaniti A, Altavilla G, Picone A, et al. Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation. Clin Exp Med 2015; 15(1): 97-105.
Berta J, Kenessey I, Dobos J, et al. Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol 2010; 5(8): 1120-9.
Heo K, Kim YH, Sung HJ, et al. Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncol 2012; 48(6): 500-6.
Sheikh AY, Chun HJ, Glassford AJ, et al. In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure. Am J Physiol Heart Circ Physiol 2008; 294(1): H88-98.
Han S, Wang G, Qi X, Lee HM, Englander EW, Greeley GH Jr. A possible role for hypoxia-induced apelin expression in enteric cell proliferation. Am J Physiol Regul Integr Comp Physiol 2008; 294(6): R1832-9.
Eyries M, Siegfried G, Ciumas M, et al. Hypoxia-induced apelin expression regulates endothelial cell proliferation and regenerative angiogenesis. Circ Res 2008; 103(4): 432-40.
Li L, Li L, Zhang Z, Jiang Z. Hypoxia promotes bone marrow-derived mesenchymal stem cell proliferation through apelin/APJ/autophagy pathway. Acta Biochim Biophys Sin 2015; 47(5): 362-7.
Kong HL, Li ZQ, Zhao SM, et al. Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes. Chin J Integr Med 2015; 21(2): 139-46.
Geiger K, Muendlein A, Stark N, et al. Hypoxia induces apelin expression in human adipocytes. Horm Metab Res 2011; 43(6): 380-5.
Lee DK, Saldivia VR, Nguyen T, Cheng R, George SR, O’Dowd BF. Modification of the terminal residue of apelin-13 antagonizes its hypotensive action. Endocrinology 2005; 146(1): 231-6.
Maloney PR, Khan P, Hedrick M, et al. Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML2 21) as a functional antagonist of the apelin (APJ) receptor. Bioorg Med Chem Lett 2012; 22(21): 6656-60.
Zhou N, Fang J, Acheampong E, Mukhtar M, Pomerantz RJ. Binding of ALX40-4C to APJ, a CNS-based receptor, inhibits its utilization as a co-receptor by HIV-1. Virology 2003; 312(1): 196-203.
Lu Q, Jiang YR, Qian J, Tao Y. Apelin-13 regulates proliferation, migration and survival of retinal Müller cells under hypoxia. Diabetes Res Clin Pract 2013; 99(2): 158-67.

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