Pseudogene OCT4-pg5 Upregulates OCT4B Expression to Promote Bladder Cancer Progression by Competing with miR-145-5p

Abstract Background Bladder cancer (BC) is one of the most common malignant neoplasms worldwide, and is characterized by metastasis and insensitivity to chemotherapy. We aim to construct competing endogenous RNA (ceRNA) networks to identify potential progression and prognostic markers associated with BC. Methods We first extracted the expression profiles of RNAs from The Cancer Genome Atlas (TCGA) database and used bioinformatic analysis to establish ceRNAs in BC. Real-time quantity PCR (RT-qPCR) was performed to measure OCT4-pg5 and OCT4B expressions in different bladder cell lines and different grades of cancer. The effects of OCT4-pg5, OCT4B and miR-145-5p on proliferation and metastasis were determined by in vitro and in vivo experiments. Luciferase reporter assay was carried out to reveal the interaction among OCT4-pg5, OCT4B and miR-145-5p. Flow cytometry was performed to explore the effects of OCT4-pg5 and OCT4B expression on the cell cycle phases distribution of T24 cells. Results The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was related to the progression and prognosis of BC. OCT4-pg5 expression was significantly increased in BC cell lines, which was correlated with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, while miR-145-5p suppressed these activities. Mechanically, OCT4-pg5 3’ untranslated region (3’UTR) competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted EMT by activating the Wnt/β-catenin pathway and upregulating the expression levels of matrix metalloproteinases (MMPs) 2 and 9 as well as transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Furthermore, elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. Conclusions These findings indicate that OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via Wnt/β-catenin pathway and enhances the cisplatin resistance. It could be prospect for the therapeutic approaches for BC.