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ABSTRACT
Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3’ untranslated region (3’UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. 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. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/β-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC.
Abbreviations
| BC | = | Bladder cancer |
| ceRNA | = | competing endogenous RNA |
| OCT4 | = | Octamer-binding transcription factor 4 |
| miR-145-5p | = | microRNA-145-5p |
| 3’UTR | = | 3’ untranslated region |
| EMT | = | Epithelial-to-mesenchymal transition |
| GDP | = | Gross Domestic Product |
| HIF | = | Hypoxia inducible factor |
| LncRNA | = | Long non-coding RNAs |
| TCGA | = | The Cancer Genome Atlas |
| BLCA | = | Bladder Urothelial Carcinoma |
| DERNAs | = | Differentially expressed RNAs |
| DElncRNAs | = | differentially expressed lncRNAs |
| DEmiRNAs | = | differentially expressed miRNAs |
| DEmRNAs | = | differentially expressed mRNAs |
| OS | = | Overall survival |
| NMIBC | = | Non-muscle-invasive bladder cancer |
| MIBC | = | Muscle-invasive bladder cancer |
Acknowledgements
We thank the patients and their families for the signed informed consent forms for clinical sample experiments. This study was supported by the Guangzhou Science and Technology Plan Project Basic and Applied Basic Research Project (202002030030), the Guangdong Province Basic and Applied Basic Research Fund Project (2020A1515010044), the National Natural Science Foundation of China (81372744), and the Japan China Sasakawa Medical Fellowship.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Authors’ contributions
Wuer Zhou, Yue Yang, and Chenglin Yang: Writing- Reviewing and Editing, Wei Wang: Investigation, Conceptualization, Supervision, Zhi Cao, Xiaoyu Lin, Huifen Zhang, Yuansong Xiao and Xiaoming Zhang: Validation. All authors reviewed the manuscript.
Data availability statement
The datasets generated and/or analyzed during the current study are available in the TCGA-BLCA, NCBI and ensemble, [https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/, and https://asia.ensembl.org/index.html].
Ethical approval and consent to participate
The study involving humans was approved by the Research Ethics Committee of General Hospital of Southern Theater Command, No. 2019–040. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. All informed consent was obtained from the subjects and guardians.
The study involving animals was approved by the Institutional Animal Care and Use Committee of the General Hospital of Southern Theater Command, No. 2019025a. The methods used in this study adhere to the tenets of the Declaration of Helsinki, and are in accordance with ARRIVE guidelines for the reporting of animal experiments.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2024.2353554