Paternally Expressed Gene 10 (PEG10) has been associated with neuroendocrine (NE)-muscle-invasive bladder cancer (MIBC), a subtype of the disease with the poorest survival. In this work, we further characterized the expression pattern of PEG10 in TCGA database of 412 MIBC pateints, and found that, compared to other subtypes, PEG10 mRNA level was enhanced in NE-like MIBC and highly correlats with other NE markers. PEG10 protein level also associated with NE markers in a tissue microarray (TMA) of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared to parental cells, and knocking-down of PEG10 re-sensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell cycle regulators p21 and p27 and delayed G1/S transition, while over-expression of PEG10 enhanced cancer cell proliferation. PEG10 silencing also lowered levels of SLUG and SNAIL, leading to reduced invasion and migration. In an orthotopic bladder cancer model, systemic treatment with PEG10 antisense oligonucleotide delayed progression of T24 xenografts. In summary, elevated expression of PEG10 in MIBC may contribute to the disease progression by promoting survival, proliferation and metastasis. Targeting PEG10 is a novel potential therapeutic approach for a subset of bladder cancers.
Molecular cancer therapeutics. 2020 Aug 26 [Epub ahead of print]
Martin E Gleave, Yoshihisa Kawai, Kenjiro Imada, Shusuke Akamatsu, Fan Zhang, Roland Seiler, Tetsutaro Hayashi, Jeffrey Leong, Eliana Beraldi, Neetu Saxena, Alexander Kretschmer, Htoo Zarni Oo, Alberto Contreras-Sanz, Hideyasu Matsuyama, Dong Lin, Ladan Fazli, Colin C Collins, Alexander W Wyatt, Peter C Black
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia ., Vancouver Prostate Centre, University of British Columbia., Department of Urology, Kyushu University., Department of Urology, Kyoto University., Urologic Sciences, University of British Columbia, The Vancouver Prostate Centre., Department of Urology, University Hospital of Bern., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia., Urologic Sciences, Vancouver Prostate Centre., Department of Urological Sciences, The Vancouver Prostate Centre., Urology, Graduate School of Medicine, Yamaguchi University., Department of Urologic Sciences, University of British Columbia, Vancouver Prostate Centre., Vancouver Prostate Centre.