RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma.
Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target.
College of Medicine and Pharmacy, Ocean University of China, Qingdao, China.|Department of Urology, 401 Hospital of PLA, Qingdao, China.
Dahai
D
Zhou
Research Institute in Healthcare Science, Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK.
Vinodh
V
Kannappan
Tangdu Hospital, Xi'an, China.
Xiang
X
Chen
Department of Urology, 401 Hospital of PLA, Qingdao, China.
Jingqin
J
Li
Department of Urology, 401 Hospital of PLA, Qingdao, China.
Xuefeng
X
Leng
Department of Urology, 401 Hospital of PLA, Qingdao, China.
Jinping
J
Zhang
College of Medicine and Pharmacy, Ocean University of China, Qingdao, China.|Qingdao Municipal Hospital, Qingdao, China.
Shiying
S
Xuan
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D054840:Retinol-Binding Proteins, Cellular / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; C518459:RBP2 protein, human; D054840:Retinol-Binding Proteins, Cellular