DOI QR코드

DOI QR Code

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

  • Liu, Bei-Bei (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Ma, Tao (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Sun, Wei (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Gao, Wu-Yue (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Liu, Jian-Min (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Li, Li-Qiang (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Li, Wen-Yong (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Wang, Sheng (Department of Urology, the First Affiliated Hospital of Bengbu Medical College) ;
  • Guo, Yuan-Yuan (Department of Urology, the First Affiliated Hospital of Bengbu Medical College)
  • Received : 2020.07.01
  • Accepted : 2020.11.23
  • Published : 2021.03.01

Abstract

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Keywords

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108. https://doi.org/10.3322/caac.21262
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29. https://doi.org/10.3322/caac.21254
  3. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66:115-132. https://doi.org/10.3322/caac.21338
  4. Huang B, Zhang J, Zhang X, Huang C, Hu G, Li S, Xie T, Liu M, Xu Y. Suppression of LETM1 by siRNA inhibits cell proliferation and invasion of bladder cancer cells. Oncol Rep. 2017;38:2935-2940. https://doi.org/10.3892/or.2017.5959
  5. Volanis D, Zaravinos A, Kadiyska T, Delakas D, Zoumpourlis V, Spandidos DA. Expression profile of Rho kinases in urinary bladder cancer. J BUON. 2011;16:511-521.
  6. Chen X, Jiang F, Jia C, Liu M, Nan Y, Qu L, Kong Q, Hou F, Luo W, Na W, Jin X, Tan J. Comprehensive gene expression analysis in NMIBC using RNA-seq reveals new therapy strategies. Front Oncol. 2019;9:523. https://doi.org/10.3389/fonc.2019.00523
  7. Wang S, Liu B, Zhang J, Sun W, Dai C, Sun W, Li Q. Centromere protein U is a potential target for gene therapy of human bladder cancer. Oncol Rep. 2017;38:735-744. https://doi.org/10.3892/or.2017.5769
  8. Zhu X, Wang D, Lin Q, Wu G, Yuan S, Ye F, Fan Q. Screening key lncRNAs for human rectal adenocarcinoma based on lncRNA-mRNA functional synergistic network. Cancer Med. 2019;8:3875-3891. https://doi.org/10.1002/cam4.2236
  9. Vecchi M, Nuciforo P, Romagnoli S, Confalonieri S, Pellegrini C, Serio G, Quarto M, Capra M, Roviaro GC, Contessini Avesani E, Corsi C, Coggi G, Di Fiore PP, Bosari S. Gene expression analysis of early and advanced gastric cancers. Oncogene. 2007;26:4284-4294. https://doi.org/10.1038/sj.onc.1210208
  10. Li H, Zhang H, Wang Y. Centromere protein U facilitates metastasis of ovarian cancer cells by targeting high mobility group box 2 expression. Am J Cancer Res. 2018;8:835-851.
  11. Pan HY, Zhang YJ, Wang XP, Deng JH, Zhou FC, Gao SJ. Identification of a novel cellular transcriptional repressor interacting with the latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J Virol. 2003;77:9758-9768. https://doi.org/10.1128/JVI.77.18.9758-9768.2003
  12. Lin SY, Lv YB, Mao GX, Chen XJ, Peng F. The effect of centromere protein U silencing by lentiviral mediated RNA interference on the proliferation and apoptosis of breast cancer. Oncol Lett. 2018;16:6721-6728.
  13. Zhang J, Zhang X, Hu Y, Li J, Liu J, Zhang S, Su W. Abstract P4-05-11: CENPU acts as a new proto-oncogene to regulate tumorigenesis and cancer metastasis in breast cancer. Cancer Res. 2015;75(9 Suppl):P4-05-11.
  14. Huang DP, Luo RC. MLF1IP is correlated with progression and prognosis in luminal breast cancer. Biochem Biophys Res Commun. 2016;477:923-926. https://doi.org/10.1016/j.bbrc.2016.06.159
  15. Hanissian SH, Teng B, Akbar U, Janjetovic Z, Zhou Q, Duntsch C, Robertson JH. Regulation of myeloid leukemia factor-1 interacting protein (MLF1IP) expression in glioblastoma. Brain Res. 2005;1047:56-64. https://doi.org/10.1016/j.brainres.2005.04.017
  16. Gopal G, Rajkumar T. Variant of mitochondrial ribosomal protein s28 (mrps28) gene is differentially expressed in response to radiation in a cervical carcinoma derived cell line. Indian J Biochem Biophys. 2005;42:81-86.
  17. Dang H, Ellis SR. Structural and functional analyses of a yeast mitochondrial ribosomal protein homologous to ribosomal protein S15 of Escherichia coli. Nucleic Acids Res. 1990;18:6895-6901. https://doi.org/10.1093/nar/18.23.6895
  18. Liang Z, Wang X, Xu X, Xie B, Ji A, Meng S, Li S, Zhu Y, Wu J, Hu Z, Lin Y, Zheng X, Xie L, Liu B. MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway. Mol Cancer. 2017;16:96. https://doi.org/10.1186/s12943-017-0664-1
  19. Suzuki H, Arakawa Y, Ito M, Saito S, Takeda N, Yamada H, Horiguchi-Yamada J. MLF1-interacting protein is mainly localized in nucleolus through N-terminal bipartite nuclear localization signal. Anticancer Res. 2007;27(3B):1423-1430.
  20. Dominguez-Valentin M, Therkildsen C, Veerla S, Jonsson M, Bernstein I, Borg A, Nilbert M. Distinct gene expression signatures in lynch syndrome and familial colorectal cancer type x. PLoS One. 2013;8:e71755. https://doi.org/10.1371/journal.pone.0071755
  21. Wang W, Jiang H, Zhu H, Zhang H, Gong J, Zhang L, Ding Q. Overexpression of high mobility group box 1 and 2 is associated with the progression and angiogenesis of human bladder carcinoma. Oncol Lett. 2013;5:884-888. https://doi.org/10.3892/ol.2012.1091
  22. Yang GL, Zhang LH, Bo JJ, Huo XJ, Chen HG, Cao M, Liu DM, Huang YR. Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer. J Surg Oncol. 2012;106:57-61. https://doi.org/10.1002/jso.23040
  23. Huang Z, Zhong Z, Zhang L, Wang X, Xu R, Zhu L, Wang Z, Hu S, Zhao X. Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway. Sci Rep. 2015;5:12807. https://doi.org/10.1038/srep12807
  24. Gao Y, Li F, Zhou H, Yang Y, Wu R, Chen Y, Li W, Li Y, Xu X, Ke C, Pei Z. Down-regulation of MRPS23 inhibits rat breast cancer proliferation and metastasis. Oncotarget. 2017;8:71772-71781. https://doi.org/10.18632/oncotarget.17888
  25. Mushtaq M, Jensen L, Davidsson S, Grygoruk OV, Andren O, Kashuba V, Kashuba E. The MRPS18-2 protein levels correlate with prostate tumor progression and it induces CXCR4-dependent migration of cancer cells. Sci Rep. 2018;8:2268. https://doi.org/10.1038/s41598-018-20765-8
  26. Sorensen KM, Meldgaard T, Melchjorsen CJ, Fridriksdottir AJ, Pedersen H, Petersen OW, Kristensen P. Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections. BMC Cancer. 2017;17:19. https://doi.org/10.1186/s12885-016-2987-5
  27. He SJ, Xiang CQ, Zhang Y, Lu XT, Chen HW, Xiong LX. Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition. Onco Targets Ther. 2017; 10:3435-3451. https://doi.org/10.2147/OTT.S139546
  28. Li Y, Gao A, Yu L. Monitoring of TGF-β 1-induced human lung adenocarcinoma A549 cells epithelial-mesenchymal transformation process by measuring cell adhesion force with a microfluidic device. Appl Biochem Biotechnol. 2016;178:114-125. https://doi.org/10.1007/s12010-015-1862-1
  29. Jia S, Wang W, Hu Z, Shan C, Wang L, Wu B, Yang Z, Yang X, Lei D. BDNF mediated TrkB activation contributes to the EMT progression and the poor prognosis in human salivary adenoid cystic carcinoma. Oral Oncol. 2015;51:64-70. https://doi.org/10.1016/j.oraloncology.2014.10.008
  30. Sun H, Liu M, Wu X, Yang C, Zhang Y, Xu Z, Gao K, Wang F. Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma. Oncol Lett. 2017;13:1725-1730. https://doi.org/10.3892/ol.2017.5645
  31. Tang Y, Weiss SJ. Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation. Cell Cycle. 2017;16:399-405. https://doi.org/10.1080/15384101.2017.1280643
  32. Jung H, Kim B, Moon BI, Oh ES. Cytokeratin 18 is necessary for initiation of TGF-β1-induced epithelial-mesenchymal transition in breast epithelial cells. Mol Cell Biochem. 2016;423:21-28. https://doi.org/10.1007/s11010-016-2818-7
  33. Jeon SY, Hwang KA, Kim CW, Jeung EB, Choi KC. Altered expression of epithelial mesenchymal transition and pluripotent associated markers by sex steroid hormones in human embryonic stem cells. Mol Med Rep. 2017;16:828-836. https://doi.org/10.3892/mmr.2017.6672

Cited by

  1. Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma vol.9, 2021, https://doi.org/10.7717/peerj.12394