Hypoxia promotes C-X-C chemokine receptor type 4 expression through microRNA-150 in pancreatic cancer cells

Sun,Jin‑Shan; Zhang,Xiao‑Lan; Yang,Yu‑Jie; Nie,Zhan‑Guo; Zhang,Yong

doi:10.3892/ol.2015.3344

Hypoxia promotes C-X-C chemokine receptor type 4 expression through microRNA-150 in pancreatic cancer cells

Authors:
- Jin‑Shan Sun
- Xiao‑Lan Zhang
- Yu‑Jie Yang
- Zhan‑Guo Nie
- Yong Zhang
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Affiliations: Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region of Chinese PLA, Urumqi, Xinjiang 830000, P.R. China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Military Region of Chinese PLA, Fuzhou, Fujian 350025, P.R. China, Department of Ophthalmology, No. 474 Hospital of Chinese PLA, Urumqi, Xinjiang 830000, P.R. China, Department of Anatomy, Histology and Embryology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: June 9, 2015 https://doi.org/10.3892/ol.2015.3344
Pages: 835-840

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Abstract

Hypoxia promotes pancreatic cancer progression by triggering cancer cell invasion. However, the mechanism underlying this process remains unclear, hindering the development of effective therapies. The present study aimed to delineate the molecular mechanisms underlying the prometastatic effect of hypoxia in pancreatic cancer cells. The expression of microRNA‑150 (miRNA‑150) was detected using reverse transcription‑quantitative polymerase chain reaction in pancreatic cancer samples and in the hypoxia‑induced CaPan2 human pancreatic cancer cell line. The target gene was identified using bioinformatics and a luciferase reporter assay. Inhibition of the expression of C‑X‑C chemokine receptor type 4 (CXCR4) by miRNA‑150 was confirmed using transfection with miRNA‑150 mimics. The prometastatic effect of hypoxia was detected using migration assays. The expression of miRNA‑150 was shown to be downregulated in pancreatic cancer samples compared with that in normal pancreatic tissue samples. Furthermore, its expression was reduced in hypoxia‑induced CaPan2 cells, compared with that in control cells. Bioinformatics and the results of the luciferase reporter assay, demonstrated that miRNA‑150 inhibited the expression of CXCR4 by directly targeting the 3' untranslated region of CXCR4 mRNA. The results of the migration assay showed that hypoxia promotes cell migration and invasion. However, this prometastatic effect was reversed by transfection with miRNA‑150 mimics. The present results suggest that hypoxia promotes pancreatic cancer migration by downregulating miRNA-150.

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1	Olson SH and Kurtz RC: Epidemiology of pancreatic cancer and the role of family history. J Surg Oncol. 107:1–7. 2013. View Article : Google Scholar : PubMed/NCBI
2	Li D and Abbruzzese JL: New strategies in pancreatic cancer: Emerging epidemiologic and therapeutic concepts. Clin Cancer Res. 16:4313–4318. 2010. View Article : Google Scholar : PubMed/NCBI
3	Li L, Li B, Chen D, Liu L, Huang C, Lu Z, Lun L and Wan X: miR-139 and miR-200c regulate pancreatic cancer endothelial cell migration and angiogenesis. Oncol Rep. 2015.(Epub ahead of print).
4	Esencay M, Sarfraz Y and Zagzag D: CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1α. BMC Cancer. 13:3472013. View Article : Google Scholar : PubMed/NCBI
5	Shen G, Li X, Jia YF, Piazza GA and Xi Y: Hypoxia-regulated microRNAs in human cancer. Acta Pharmacol Sin. 34:336–341. 2013. View Article : Google Scholar : PubMed/NCBI
6	Noman MZ, Buart S, Romero P, et al: Hypoxia-inducible miR-210 regulates the susceptibility of tumor cells to lysis by cytotoxic T cells. Cancer Res. 72:4629–4641. 2012. View Article : Google Scholar : PubMed/NCBI
7	Pocock R: Invited review: Decoding the microRNA response to hypoxia. Pflugers Arch. 461:307–315. 2011. View Article : Google Scholar : PubMed/NCBI
8	Bruning U, Cerone L, Neufeld Z, et al: MicroRNA-155 promotes resolution of hypoxia-inducible factor 1 alpha activity during prolonged hypoxia. Mol Cell Biol. 31:4087–4096. 2011. View Article : Google Scholar : PubMed/NCBI
9	Yu ZY, Bai YN, Luo LX, Wu H and Zeng Y: Expression of microRNA-150 targeting vascular endothelial growth factor-A is downregulated under hypoxia during liver regeneration. Mol Med Rep. 8:287–293. 2013.PubMed/NCBI
10	Chen C, Ridzon DA, Broomer AJ, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
11	Hurley J, Roberts D, Bond A, Keys D and Chen C: Stem-loop RT-qPCR for microRNA expression profiling. Methods Mol Biol. 822:33–52. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zhou L, Wang DS, Li QJ, Sun W, Zhang Y and Dou KF: The down-regulation of Notch1 inhibits the invasion and migration of hepatocellular carcinoma cells by inactivating the cyclooxygenase-2/Snail/E-cadherin pathway in vitro. Dig Dis Sci. 58:1016–1025. 2013. View Article : Google Scholar : PubMed/NCBI
13	Oh YS, Kim HY, Song IC, Yun HJ, Jo DY, Kim S and Lee HJ: Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α. Oncol Rep. 28:2239–2246. 2012.PubMed/NCBI
14	Srivastava SK, Bhardwaj A, Singh S, et al: MicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cells. Carcinogenesis. 32:1832–1839. 2011. View Article : Google Scholar : PubMed/NCBI
15	Sikand K, Slaibi JE, Singh R, Slane SD and Shukla GC: miR 488* inhibits androgen receptor expression in prostate carcinoma cells. Int J Cancer. 129:810–819. 2011. View Article : Google Scholar : PubMed/NCBI
16	Sachdeva M and Mo YY: MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res. 70:378–387. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Fei M, Xue G, et al: Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: New insights into molecular mechanisms for the disease. J Cell Mol Med. 16:249–259. 2012. View Article : Google Scholar : PubMed/NCBI
18	Biswas S, Roy S, Banerjee J, et al: Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds. Proc Natl Acad Sci USA. 107:6976–6981. 2010. View Article : Google Scholar : PubMed/NCBI
19	Ying Q, Liang L, Guo W, et al: Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology. 54:2064–2075. 2011. View Article : Google Scholar : PubMed/NCBI
20	Liu T, Zhao L, Chen W, Li Z, Hou H, Ding L and Li X: Inactivation of von Hippel-Lindau increases ovarian cancer cell aggressiveness through the HIF1α/miR-210/VMP1 signaling pathway. Int J Mol Med. 33:1236–1242. 2014.PubMed/NCBI