HIF-1α inhibits IDH-1 expression in osteosarcoma

Liu,Deng-Cheng; Zheng,Xun; Zho,Yong; Yi,Wan-Rong; Li,Zong-Huan; Hu,Xiang; Yu,Ai-Xi

doi:10.3892/or.2017.5655

HIF-1α inhibits IDH-1 expression in osteosarcoma

Authors:
- Deng-Cheng Liu
- Xun Zheng
- Yong Zho
- Wan-Rong Yi
- Zong-Huan Li
- Xiang Hu
- Ai-Xi Yu
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Affiliations: Zhongnan Hospital of Wuhan University, Department of Orthopedics, Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: May 22, 2017 https://doi.org/10.3892/or.2017.5655
Pages: 336-342

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Abstract

Recently, hypoxia inducible factor-1 (HIF-1) was reported to be correlated with isocitrate dehydrogenase 1 (IDH-1) in several types of tumors. However, the expression and significance of HIF-1 and IDH-1 in osteosarcoma is still unknown. In the present study, the expression levels of IDH-1 and HIF-1α in 35 formalin-fixed paraffin-embedded sections from osteosarcoma patients were investigated by immunohistochemistry. The expression levels of IDH-1 and HIF-1α in human osteosarcoma cell lines (MG-63 and 143B) were further detected by western blotting under normal and hypoxic conditions. In addition, HIF-1α was downregulated via lentiviral vector‑mediated RNA interference (RNAi) in the MG-63 human osteosarcoma cell line. The results revealed that HIF-1α was negatively correlated with IDH-1 in the osteosarcoma tissues. Both in MG-63 and 143B cell lines, the expression of HIF-1α was increased while IDH-1 was decreased under a hypoxic condition compared to normal conditions. HIF-1α downregulation promoted IDH-1 expression in the MG-63 cell line under either normal or hypoxic conditions. In conclusion, our findings suggest that HIF-1α inhibits IDH-1 in osteosarcoma and consequently increases the incidence of osteosarcoma.

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1	Anderson ME: Update on survival in osteosarcoma. Orthop Clin North Am. 47:283–292. 2016. View Article : Google Scholar : PubMed/NCBI
2	Duchman KR, Gao Y and Miller BJ: Prognostic factors for survival in patients with high-grade osteosarcoma using the Surveillance, Epidemiology, and End Results (SEER) Program database. Cancer Epidemiol. 39:593–599. 2015. View Article : Google Scholar : PubMed/NCBI
3	Rosen G: Preoperative (neoadjuvant) chemotherapy for osteogenic sarcoma: A ten year experience. Orthopedics. 8:659–664. 1985.PubMed/NCBI
4	Lendahl U, Lee KL, Yang H and Poellinger L: Generating specificity and diversity in the transcriptional response to hypoxia. Nat Rev Genet. 10:821–832. 2009. View Article : Google Scholar : PubMed/NCBI
5	Wang GL and Semenza GL: Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem. 268:21513–21518. 1993.PubMed/NCBI
6	Parks SK, Chiche J and Pouysségur J: Disrupting proton dynamics and energy metabolism for cancer therapy. Nat Rev Cancer. 13:611–623. 2013. View Article : Google Scholar : PubMed/NCBI
7	Li N, Li Y, Li Z, Huang C, Yang Y, Lang M, Cao J, Jiang W, Xu Y, Dong J, et al: Hypoxia inducible factor 1 (HIF-1) recruits macrophage to activate pancreatic stellate cells in pancreatic ductal adenocarcinoma. Int J Mol Sci. 17:172016.
8	Mouriaux F, Sanschagrin F, Diorio C, Landreville S, Comoz F, Petit E, Bernaudin M, Rousseau AP, Bergeron D and Morcos M: Increased HIF-1α expression correlates with cell proliferation and vascular markers CD31 and VEGF-A in uveal melanoma. Invest Ophthalmol Vis Sci. 55:1277–1283. 2014. View Article : Google Scholar : PubMed/NCBI
9	Guo M, Cai C, Zhao G, Qiu X, Zhao H, Ma Q, Tian L, Li X, Hu Y, Liao B, et al: Hypoxia promotes migration and induces CXCR4 expression via HIF-1α activation in human osteosarcoma. PLoS One. 9:e905182014. View Article : Google Scholar : PubMed/NCBI
10	Zhan H, Liang H, Liu X, Deng J, Wang B and Hao X: Expression of Rac1, HIF-1α, and VEGF in gastric carcinoma: Correlation with angiogenesis and prognosis. Onkologie. 36:102–107. 2013. View Article : Google Scholar : PubMed/NCBI
11	Marton I, Knezevic F, Ramic S, Milosevic M and Tomas D: Immunohistochemical expression and prognostic significance of HIF-1α and VEGF-C in neuroendocrine breast cancer. Anticancer Res. 32:5227–5232. 2012.PubMed/NCBI
12	Kaelin WG Jr: How oxygen makes its presence felt. Genes Dev. 16:1441–1445. 2002. View Article : Google Scholar : PubMed/NCBI
13	Nekrutenko A, Hillis DM, Patton JC, Bradley RD and Baker RJ: Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family. Mol Biol Evol. 15:1674–1684. 1998. View Article : Google Scholar : PubMed/NCBI
14	Boisselier B, Gállego Pérez-Larraya J, Rossetto M, Labussière M, Ciccarino P, Marie Y, Delattre JY and Sanson M: Detection of IDH1 mutation in the plasma of patients with glioma. Neurology. 79:1693–1698. 2012. View Article : Google Scholar : PubMed/NCBI
15	Shechter I, Dai P, Huo L and Guan G: IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells: Evidence that IDH1 may regulate lipogenesis in hepatic cells. J Lipid Res. 44:2169–2180. 2003. View Article : Google Scholar : PubMed/NCBI
16	Memon AA, Chang JW, Oh BR and Yoo YJ: Identification of differentially expressed proteins during human urinary bladder cancer progression. Cancer Detect Prev. 29:249–255. 2005. View Article : Google Scholar : PubMed/NCBI
17	Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, et al: Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science. 324:261–265. 2009. View Article : Google Scholar : PubMed/NCBI
18	Hu X, Liu Y, Qin C, Pan Z, Luo J, Yu A and Cheng Z: Up-regulated isocitrate dehydrogenase 1 suppresses proliferation, migration and invasion in osteosarcoma: In vitro and in vivo. Cancer Lett. 346:114–121. 2014. View Article : Google Scholar : PubMed/NCBI
19	Lv F, Du R, Shang W, Suo S, Yu D and Zhang J: HIF-1α silencing inhibits the growth of osteosarcoma cells by inducing apoptosis. Ann Clin Lab Sci. 46:140–146. 2016.PubMed/NCBI
20	Roncuzzi L, Pancotti F and Baldini N: Involvement of HIF-1α activation in the doxorubicin resistance of human osteosarcoma cells. Oncol Rep. 32:389–394. 2014.PubMed/NCBI
21	Zhang B, Guo W, Yu L, Wang F, Xu Y, Liu Y and Huang C: Cobalt chloride inhibits tumor formation in osteosarcoma cells through upregulation of HIF-1α. Oncol Lett. 5:911–916. 2013.PubMed/NCBI
22	Hu X, Yu AX, Qi BW, Fu T, Wu G, Zhou M, Luo J and Xu JH: The expression and significance of IDH1 and p53 in osteosarcoma. J Exp Clin Cancer Res. 29:432010. View Article : Google Scholar : PubMed/NCBI
23	Usnarska-Zubkiewicz L, Mazur G, Wróbel T, Poreba M and Kuliczkowski K: Expression of serum vascular endothelial growth factor correlates with clinical outcome in multiple myeloma. Pol Arch Med Wewn. 110:719–724. 2003.(In Polish). PubMed/NCBI
24	Wu L, Peng CW, Hou JX, Zhang YH, Chen C, Chen LD and Li Y: Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation. J Exp Clin Cancer Res. 29:172010. View Article : Google Scholar : PubMed/NCBI
25	Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T, Lin BK, Gupta D, Shima Y, Chauhan D, et al: Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood. 98:428–435. 2001. View Article : Google Scholar : PubMed/NCBI
26	Oda S, Oda T, Nishi K, Takabuchi S, Wakamatsu T, Tanaka T, Adachi T, Fukuda K, Semenza GL and Hirota K: Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner. PLoS One. 3:e22152008. View Article : Google Scholar : PubMed/NCBI
27	Neal CS, Michael MZ, Rawlings LH, Van der Hoek MB and Gleadle JM: The VHL-dependent regulation of microRNAs in renal cancer. BMC Med. 8:642010. View Article : Google Scholar : PubMed/NCBI
28	Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F, Pollock R, ODonnell P, Grigoriadis A, Diss T, et al: IDH1IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol. 224:334–343. 2011. View Article : Google Scholar : PubMed/NCBI
29	MacKenzie ED, Selak MA, Tennant DA, Payne LJ, Crosby S, Frederiksen CM, Watson DG and Gottlieb E: Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol Cell Biol. 27:3282–3289. 2007. View Article : Google Scholar : PubMed/NCBI
30	Ingebretsen OC: Mechanism of the inhibitory effect of glyoxylate plus oxaloacetate and oxalomalate on the NADP-specific isocitrate dehydrogenase. Biochim Biophys Acta. 452:302–309. 1976. View Article : Google Scholar : PubMed/NCBI
31	Krell D, Mulholland P, Frampton AE, Krell J, Stebbing J and Bardella C: IDH mutations in tumorigenesis and their potential role as novel therapeutic targets. Future Oncol. 9:1923–1935. 2013. View Article : Google Scholar : PubMed/NCBI
32	Yang X, Du T, Wang X, Zhang Y, Hu W, Du X, Miao L and Han C: IDH1, a CHOP and C/EBPβ-responsive gene under ER stress, sensitizes human melanoma cells to hypoxia-induced apoptosis. Cancer Lett. 365:201–210. 2015. View Article : Google Scholar : PubMed/NCBI
33	Semenza GL: Expression of hypoxia-inducible factor 1: Mechanisms and consequences. Biochem Pharmacol. 59:47–53. 2000. View Article : Google Scholar : PubMed/NCBI
34	Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al: Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 481:380–384. 2011.PubMed/NCBI
35	Jang BC: The fruit juice of Morinda citrifolia (noni) downregulates HIF-1α protein expression through inhibition of PKB, ERK-1/2, JNK-1 and S6 in manganese-stimulated A549 human lung cancer cells. Int J Mol Med. 29:499–504. 2012.PubMed/NCBI
36	Qian J, Bai H, Gao Z, Dong YU, Pei J, Ma M and Han B: Downregulation of HIF-1α inhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells. Oncol Lett. 11:1738–1744. 2016.PubMed/NCBI
37	Akakura N, Kobayashi M, Horiuchi I, Suzuki A, Wang J, Chen J, Niizeki H, Kawamura Ki, Hosokawa M and Asaka M: Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation. Cancer Res. 61:6548–6554. 2001.PubMed/NCBI
38	Krishnamachary B, Berg-Dixon S, Kelly B, Agani F, Feldser D, Ferreira G, Iyer N, LaRusch J, Pak B, Taghavi P, et al: Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 63:1138–1143. 2003.PubMed/NCBI