The oncoprotein hepatitis B X-interacting protein promotes the migration of ovarian cancer cells through the upregulation of S-phase kinase-associated protein 2 by Sp1.
Hepatitis B X-interacting protein (HBXIP) is a novel oncoprotein. We have previously reported that HBXIP promotes the proliferation and migration of breast cancer cells. S-phase kinase-associated protein 2 (Skp2) is another oncoprotein which is important for migration. In this study, we investigated whether Skp2 is involved in the migration enhanced by HBXIP in ovarian cancer. The expression of HBXIP and Skp2 in ovarian cancer tissues was examined by immunohistochemistry using tissue microarrays. The role of HBXIP and Skp2 in the migration of ovarian cancer cells was investigated by wound-healing assay and Transwell migration assay. The effect of HBXIP on Skp2 was assessed by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, luciferase reporter gene assays and chromatin immunoprecipitation in ovarian cancer cells (SKOV3 and CAOV3). We found that both HBXIP and Skp2 were highly expressed in ovarian cancer tissues. We observed that the overexpression of HBXIP enhanced the migration of ovarian cancer cells, while Skp2 siRNAs decreased the cell migration enhanced by HBXIP. The HBXIP siRNAs inhibited ovarian cancer cell migration and Skp2 rescued the migration inhibition induced by HBXIP siRNA. HBXIP could upregulate Skp2 at the levels of mRNA and protein in ovarian cancer cells. Moreover, HBXIP increased the activity of Skp2 promoter via binding to the transcription factor Sp1. HBXIP is highly expressed in ovarian cancer tissues. HBXIP enhances the migration of ovarian cancer cells. HBXIP was able to stimulate the activity of Skp2 promoter via transcription factor Sp1 thus promoting the migration of ovarian cancer cells.
Department of Gynecology and Obstetrics, General Hospital Chinese PLA, Beijing 100853, P.R. China.
Fuqiang
F
Xu
Department of Gynecology and Obstetrics, General Hospital Chinese PLA, Beijing 100853, P.R. China.
Xiaoming
X
Zhu
Department of Orthopedics, Hainan Branch of PLA General Hospital, Sanya, Hainan 572013, P.R. China.
Tao
T
Han
Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
Xiaona
X
You
Department of Biochemistry, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
Fabao
F
Liu
Department of Biochemistry, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
Lihong
L
Ye
Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
Xiaodong
X
Zhang
Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China.
Xiaohong
X
Wang
Department of Gynecology and Obstetrics, General Hospital Chinese PLA, Beijing 100853, P.R. China.
Yuanqing
Y
Yao
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D011401:Promoter Regions, Genetic; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis
D048868:Adaptor Proteins, Signal Transducing; C110719:LAMTOR5 protein, human; D044786:S-Phase Kinase-Associated Proteins; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human