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Cellular Oncology

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14-11-2022 | Original Article

CEP55 3’-UTR promotes epithelial–mesenchymal transition and enhances tumorigenicity of bladder cancer cells by acting as a ceRNA regulating miR-497-5p

Authors: Chenglin Yang, Yue Yang, Wei Wang, Wuer Zhou, Xiaoming Zhang, Yuansong Xiao, Huifen Zhang

Published in: Cellular Oncology | Issue 6/2022

Abstract

Background

Centrosomal protein 55 (CEP55) is implicated in the tumorigenesis of bladder cancer (BC) but the detailed molecular mechanisms are unknown. We aim to develop a potential competing endogenous RNA (ceRNA) network related with CEP55 in 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) and immunohistochemical analysis were performed to measure CEP55 expression in different bladder cell lines and different grades of cancer. Bioinformatics analysis and luciferase assays were conducted to predict potential binding sites among miR-497-5p, CEP55, parathyroid hormone like hormone (PTHLH) and high mobility group A2 (HMGA2). Tumor xenograft model was used to show the effect of CEP55 3’-UTR on cisplatin therapy. Bioinformatics analysis, luciferase assays, and 5' rapid amplification of cDNA ends (5’RACE) were to explore the function of CEP55 3’-untranslated region (3’-UTR) on targeting miR-497-5p. Western blot and immunofluorescence assays were to detect the epithelial–mesenchymal transition (EMT) induction of CEP55 3’-UTR.

Results

CEP55 expression as well as the expression levels of the oncogenic proteins PTHLH and HMGA2 were upregulated in BC cells while miR-497-5p was downregulated. Low miR-497-5p expression and high CEP55 and HMGA2 expression levels were associated with more advanced tumor clinical stage and pathological grade. Overexpression of the CEP55 3’-UTR promoted the proliferation, migration, and invasion of the EJ cell line in vitro and accelerated EJ-derived tumor growth in nude mice, while inhibition of the CEP55 3’-UTR suppressed all of these oncogenic processes. In addition, CEP55 3’-UTR upregulation reduced the cisplatin sensitivity of BC cell lines and xenograft tumors. Bioinformatics analysis, luciferase assays, and 5’RACE suggested that the CEP55 3’-UTR functions as a ceRNA targeting miR-497-5p, leading to miR-497-5p downregulation and disinhibition of PTHLH and HMGA2 expression. Further, CEP55 downregulated miR-497-5p transcription by promoting NF-\(\kappa\)B signaling. In turn, CEP55 3’-UTR ultimately promotes EMT and tumorigenesis by activating P38MAPK and ERK 1/2 pathways.

Conclusions

These results suggest that a ceRNA regulatory network involving CEP55 upregulates PTHLH and HMGA2 expression by suppressing endogenous miR-497-5p. We unveiled a novel mechanism of BC metastasis, and could become novel therapeutics targets in BC.

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Title: CEP55 3’-UTR promotes epithelial–mesenchymal transition and enhances tumorigenicity of bladder cancer cells by acting as a ceRNA regulating miR-497-5p
Authors: Chenglin Yang
Yue Yang
Wei Wang
Wuer Zhou
Xiaoming Zhang
Yuansong Xiao
Huifen Zhang
Publication date: 14-11-2022
Publisher: Springer Netherlands
Published in: Cellular Oncology / Issue 6/2022
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-022-00712-6

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Abstract

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Conclusions

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