title: Hypoxia promotes C-X-C chemokine receptor type 4 expression through microRNA-150 in pancreatic cancer cells.
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.
authors.affiliation: Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region of Chinese PLA, Urumqi, Xinjiang 830000, P.R. China.
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Fuzhou General Hospital of Nanjing Military Region of Chinese PLA, Fuzhou, Fujian 350025, P.R. China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, No. 474 Hospital of Chinese PLA, Urumqi, Xinjiang 830000, P.R. China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region of Chinese PLA, Urumqi, Xinjiang 830000, P.R. China.
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Nie
authors.affiliation: Department of Anatomy, Histology and Embryology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
keywords: C-X-C chemokine receptor type 4; hypoxia; miRNA-150; pancreatic cancer