title: Osteopontin enhances the expression of HOTAIR in cancer cells via IRF1.
abstract: Osteopontin (OPN), a secreted phosphoglycoprotein, plays important roles in tumor growth, invasion, and metastasis for many types of cancers. The long, noncoding RNA HOTAIR has been strongly associated with the invasion and metastasis of cancer cells. In this study, we found that recombinant human OPN could induce HOTAIR expression in a time- and dose-dependent manner, and our data also showed that OPN transcriptionally activated the expression of HOTAIR in cancer cells. Furthermore, through chromatin immunoprecipitation and luciferase activity assays, we found that IRF1 could bind to the HOTAIR promoter region and decrease its transcriptional activity, and cellular overexpression of IRF1 downregulated the level of HOTAIR. The receptor CD44 has also been verified as a regulator of OPN-induced HOTAIR expression. Interestingly, our data demonstrated that OPN could regulate PI3K/AKT and IRF1 expression and signaling, thereby influencing the expression of HOTAIR. In hepatocellular carcinoma samples, levels of HOTAIR correlated with the expression of OPN and IRF1. We therefore conclude that OPN, as an extracellular matrix protein, can stimulate the expression of HOTAIR by attenuating the inhibitory effect of IRF1, and this results in promotion of the invasion and metastasis of cancer cells.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shenghong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Zhenyin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Mingjian
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Imaging and Interventional Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China. Electronic address: zhangfj@sysucc.org.cn.
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053495:Osteopontin / Q000235:genetics / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C497483:CD44 protein, human; C561566:HOTAIR long untranslated RNA, human; D018960:Hyaluronan Receptors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D062085:RNA, Long Noncoding; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cancer cells; HOTAIR; IRF1; Osteopontin