MicroRNA‑210 knockdown contributes to apoptosis caused by oxygen glucose deprivation in PC12 cells

Qiu,Jie; Zhou,Xiao‑Yu; Zhou,Xiao‑Guang; Li,Yong; Cheng,Rui; Liu,Hai‑Ying

doi:10.3892/mmr.2014.2651

MicroRNA‑210 knockdown contributes to apoptosis caused by oxygen glucose deprivation in PC12 cells

Authors:
- Jie Qiu
- Xiao‑Yu Zhou
- Xiao‑Guang Zhou
- Yong Li
- Rui Cheng
- Hai‑Ying Liu
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Affiliations: Department of Newborn Infants, Nanjing Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China, Department of Newborn Infants, Nanjing Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
Published online on: October 15, 2014 https://doi.org/10.3892/mmr.2014.2651
Pages: 719-723

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Abstract

It was previously demonstrated that microRNA-210 (miR-210) exhibited neuroprotective effects in a murine model of hypoxic‑ischemic encephalopathy via inhibition of apoptosis. The aim of the present study was to further elucidate the effect of miR-210 on apoptosis in PC12 cells following transfection with miR‑210 inhibitors and exposure to oxygen glucose deprivation (OGD). The expression levels of miR‑210 were identified using reverse transcription‑quantitative polymerase chain reaction analysis. Apoptosis was investigated using Annexin V‑fluorescein isothiocyanate assays. Apoptosis‑related protein expression levels were studied with western blot analysis. The results showed that the expression levels of miR‑210 were upregulated in PC12 cells following a 4‑h exposure to OGD, relative to those in normoxic control cells. miR‑210 knockdown increased cell apoptosis by inducing caspase activity and regulating the balance between Bcl‑2 and Bax levels. The present study demonstrated that miR‑210 knockdown induced cell apoptosis using an ex vivo model of ischemic hypoxia (IH). Knockdown of miR‑210 represents a potential novel therapeutic approach to combat neonatal IH.

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1	Tioseco JA, Aly H, Essers J, Patel K and El-Mohandes AA: Male sex and intraventricular hemorrhage. Pediatr Crit Care Med. 7:40–44. 2006. View Article : Google Scholar : PubMed/NCBI
2	du Plessis AJ and Volpe JJ: Perinatal brain injury in the preterm and term newborn. Curr Opin Neurol. 15:151–157. 2002.PubMed/NCBI
3	Ivan M, Harris AL, Martelli F and Kulshreshtha R: Hypoxia response and microRNAs: no longer two separate worlds. J Cell Mol Med. 12:1426–1431. 2008. View Article : Google Scholar : PubMed/NCBI
4	Chan SY and Loscalzo J: MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle. 9:1072–1083. 2010. View Article : Google Scholar : PubMed/NCBI
5	Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL and Loscalzo J: MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 10:273–284. 2009. View Article : Google Scholar : PubMed/NCBI
6	Chen Z, Li Y, Zhang H, Huang P and Luthra R: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene. 29:4362–4368. 2010. View Article : Google Scholar : PubMed/NCBI
7	Favaro E, Ramachandran A, McCormick R, Gee H, et al: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PloS One. 5:e103452010. View Article : Google Scholar : PubMed/NCBI
8	Huang X, Ding L, Bennewith KL, Tong RT, et al: Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell. 35:856–867. 2009. View Article : Google Scholar : PubMed/NCBI
9	Kushibiki T: Photodynamic therapy induces microRNA-210 and -296 expression in HeLa cells. J Biophotonics. 3:368–372. 2010. View Article : Google Scholar : PubMed/NCBI
10	Pulkkinen K, Malm T, Turunen M, Koistinaho J and Yla-Herttualä S: Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210. FEBS Lett. 582:2397–2401. 2008. View Article : Google Scholar : PubMed/NCBI
11	Bacon AL and Harris AL: Hypoxia-inducible factors and hypoxic cell death in tumour physiology. Ann Med. 36:530–539. 2004. View Article : Google Scholar : PubMed/NCBI
12	Gordan JD and Simon MC: Hypoxia-inducible factors: central regulators of the tumor phenotype. Curr Opin Genet Dev. 17:71–77. 2007. View Article : Google Scholar : PubMed/NCBI
13	Gruber M and Simon MC: Hypoxia-inducible factors, hypoxia, and tumor angiogenesis. Curr Opin Hematol. 13:169–174. 2006. View Article : Google Scholar : PubMed/NCBI
14	Harris AL: Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI
15	Kim JW, Tchernyshyov I, Semenza GL and Dang CV: HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3:177–185. 2006. View Article : Google Scholar : PubMed/NCBI
16	Koumenis C: ER stress, hypoxia tolerance and tumor progression. Curr Mol Med. 6:55–69. 2006. View Article : Google Scholar : PubMed/NCBI
17	Qiu J, Zhou XY, Zhou XG, Cheng R, Liu HY and Li Y: Neuroprotective effects of microRNA-210 against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells. Mol Med Rep. 7:1955–1959. 2013.PubMed/NCBI
18	Tabakman R, Lazarovici P and Kohen R: Neuroprotective effects of carnosine and homocarnosine on pheochromocytoma PC12 cells exposed to ischemia. Journal Neurosci Res. 68:463–469. 2002. View Article : Google Scholar : PubMed/NCBI
19	Guo G and Bhat NR: p38alpha MAP kinase mediates hypoxia-induced motor neuron cell death: a potential target of minocycline’s neuroprotective action. Neurochem Res. 32:2160–2166. 2007.PubMed/NCBI
20	Tabakman R, Jiang H, Schaefer E, Levine RA and Lazarovici P: Nerve growth factor pretreatment attenuates oxygen and glucose deprivation-induced c-Jun amino-terminal kinase 1 and stress-activated kinases p38alpha and p38beta activation and confers neuroprotection in the pheochromocytoma PC12 model. J Mol Neurosci. 22:237–250. 2004. View Article : Google Scholar
21	Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM and Ruvkun G: Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Nat Acad Sci USA. 101:360–365. 2004. View Article : Google Scholar : PubMed/NCBI
22	Kosik KS and Krichevsky AM: The elegance of the microRNAs: A neuronal perspective. Neuron. 47:779–782. 2005. View Article : Google Scholar : PubMed/NCBI
23	Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M and Greenberg ME: A brain-specific microRNA regulates dendritic spine development. Nature. 439:283–289. 2006. View Article : Google Scholar : PubMed/NCBI
24	Qiu J, Zhou XY, Zhou XG, Cheng R, Liu HY and Li Y: Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy. Biomed Res Int. 2013:3504192013.PubMed/NCBI
25	Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, et al: MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem. 283:15878–15883. 2008. View Article : Google Scholar : PubMed/NCBI
26	Giannakakis A, Sandaltzopoulos R, Greshock J, Liang S, Huang J, Hasegawa K, Li C, O’Brien-Jenkins A, Katsaros D, Weber BL, Simon C, Coukos G and Zhang L: miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther. 7:255–264. 2008. View Article : Google Scholar : PubMed/NCBI
27	van Rooij E, Liu N and Olson EN: MicroRNAs flex their muscles. Trends Genet. 24:159–166. 2008.
28	Love TM, Moffett HF and Novina CD: Not miR-ly small RNAs: big potential for microRNAs in therapy. J Allergy Clin Immunol. 121:309–319. 2008. View Article : Google Scholar : PubMed/NCBI
29	Weiler J, Hunziker J and Hall J: Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther. 13:496–502. 2006. View Article : Google Scholar
30	Ørom UA, Kauppinen S and Lund AH: LNA modified oligonucleotides mediate specific inhibition of microRNA function. Gene. 372:137–141. 2006.PubMed/NCBI
31	Zhang B and Farwell MA: microRNAs: a new emerging class of players for disease diagnostics and gene therapy. J Cell Mol Med. 12:3–21. 2008. View Article : Google Scholar : PubMed/NCBI
32	Liu NK and Xu XM: MicroRNA in central nervous system trauma and degenerative disorders. Physiol Genomics. 43:571–580. 2011. View Article : Google Scholar : PubMed/NCBI
33	Zhang C: Novel functions for small RNA molecules. Curr Opin Mol Ther. 11:641–651. 2009.PubMed/NCBI