CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer

Wang,Xue-Xuan; Wu,Hua-Yu; Yang,Ying; Ma,Miao-Miao; Zhang,Yi-Wei; Huang,Hai-Zhen; Li,Sheng-Hua; Pan,Shang-Ling; Tang,Jun; Peng,Jun-Hua

doi:10.3892/etm.2023.12081

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer

Authors:
- Xue-Xuan Wang
- Hua-Yu Wu
- Ying Yang
- Miao-Miao Ma
- Yi-Wei Zhang
- Hai-Zhen Huang
- Sheng-Hua Li
- Shang-Ling Pan
- Jun Tang
- Jun-Hua Peng
View Affiliations

Affiliations: Department of Pathophysiology, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Medical Experimental Center, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530022, P.R. China, Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: June 27, 2023 https://doi.org/10.3892/etm.2023.12081
Article Number: 382
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1‑transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh‑CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh‑CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26‑2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh‑CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh‑CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

View Figures

View References

1	Xu Y, Wu G, Li J, Li J, Ruan N, Ma L, Han X, Wei Y, Li L, Zhang H, et al: Screening and identification of key biomarkers for bladder cancer: A study based on TCGA and GEO Data. Biomed Res Int. 82(83401)2020.PubMed/NCBI View Article : Google Scholar
2	Schlack K, Boegemann M, Steinestel J, Schrader A and Krabbe L: The safety and efficacy of gemcitabine for the treatment of bladder cancer. Expert Rev Anticancer Ther. 16:255–271. 2016.PubMed/NCBI View Article : Google Scholar
3	Shi S and Tian B: Identification of biomarkers associated with progression and prognosis in bladder cancer via co-expression analysis. Cancer Biomark. 24:183–193. 2019.PubMed/NCBI View Article : Google Scholar
4	Cao R, Yuan L, Ma B, Wang G, Qiu W and Tian Y: An EMT-related gene signature for the prognosis of human bladder cancer. J Cell Mol Med. 24:605–617. 2020.PubMed/NCBI View Article : Google Scholar
5	Xie B, Wang S, Jiang N and Li JJ: Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance. Cancer Lett. 443:56–66. 2019.PubMed/NCBI View Article : Google Scholar
6	Petrachkova T, Wortinger LA, Bard AJ, Singh J, Warga R and Kane D: Lack of Cyclin B1 in zebrafish causes lengthening of G2 and M phases. Dev Biol. 451:167–179. 2019.PubMed/NCBI View Article : Google Scholar
7	Marques HP, da Silva SG, De Martin E, Agopian VG and Martins PN: Emerging biomarkers in HCC patients: Current status. Int J Surg. 82s:70–76. 2020.PubMed/NCBI View Article : Google Scholar
8	Zhang H, Zhang X, Li X, Meng WB, Bai ZT, Rui SZ, Wang ZF, Zhou WC and Jin XD: Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer. J Cell Physiol. 234:619–631. 2018.PubMed/NCBI View Article : Google Scholar
9	Fang Y, Yu H, Liang X, Xu J and Cai X: Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer. Cancer Biol Ther. 15:1268–1279. 2014.PubMed/NCBI View Article : Google Scholar
10	Zou Y, Ruan S, Jin L, Chen Z, Han H, Zhang Y, Jian Z, Lin Y, Shi N and Jin H: CDK1, CCNB1, and CCNB2 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma. Med Sci Monit. 26(e925289)2020.PubMed/NCBI View Article : Google Scholar
11	Hu L, Pan X, Hu J, Zeng H, Liu X, Jiang M and Jiang B: Proteasome inhibitors decrease paclitaxel-induced cell death in nasopharyngeal carcinoma with the accumulation of CDK1/cyclin B1. Int J Mol Med. 48(193)2021.PubMed/NCBI View Article : Google Scholar
12	Zeng S, Yu X, Ma C, Song R, Zhang Z, Zi X, Chen X, Wang Y, Yu Y, Zhao J, et al: Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma. Sci Rep. 7(3151)2017.PubMed/NCBI View Article : Google Scholar
13	Wu F, Sun Y, Chen J, Li H, Yao K, Liu Y, Liu Q and Liu J: The oncogenic role of APC/C activator protein Cdc20 by an integrated pan-cancer analysis in human tumors. Front Oncol. 11(721797)2021.PubMed/NCBI View Article : Google Scholar
14	Dobruch J and Oszczudłowski M: Bladder cancer: Current challenges and future directions. Medicina (Kaunas). 57(749)2021.PubMed/NCBI View Article : Google Scholar
15	Jamasbi E, Hamelian M, Hossain MA and Varmira K: The cell cycle, cancer development and therapy. Mol Biol Rep. 49:10875–10883. 2022.PubMed/NCBI View Article : Google Scholar
16	Fang L, Du WW, Awan FM, Dong J and Yang BB: The circular RNA circ-Ccnb1 dissociates Ccnb1/Cdk1 complex suppressing cell invasion and tumorigenesis. Cancer Lett. 459:216–226. 2019.PubMed/NCBI View Article : Google Scholar
17	Chen EB, Qin X, Peng K, Li Q, Tang C, Wei YC, Yu S, Gan L and Liu T: HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis. Aging (Albany NY). 11:7473–7491. 2019.PubMed/NCBI View Article : Google Scholar
18	Li Y, Ji S, Fu LY, Jiang T, Wu D and Meng FD: Knockdown of cyclin-dependent kinase inhibitor 3 inhibits proliferation and invasion in human gastric cancer cells. Oncol Res. 25:721–731. 2017.PubMed/NCBI View Article : Google Scholar
19	Yang X, Zhou S, Yang C, Cao C, He M and Zi S: CCNB1, negatively regulated by miR-559, promotes the proliferation, migration, and invasion of ovarian carcinoma cells. Mol Biotechnol. 64:958–969. 2022.PubMed/NCBI View Article : Google Scholar
20	Gu J, Liu X, Li J and He Y: MicroRNA-144 inhibits cell proliferation, migration and invasion in human hepatocellular carcinoma by targeting CCNB1. Cancer Cell Int. 19(15)2019.PubMed/NCBI View Article : Google Scholar
21	Song Y, Zhao C, Dong L, Fu M, Xue L, Huang Z, Tong T, Zhou Z, Chen A, Yang Z, et al: Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis. Carcinogenesis. 29:307–315. 2008.PubMed/NCBI View Article : Google Scholar
22	Sun J, Du Y, Song Q, Nan J, Guan PZ, Guo JH, Wang X, Yang JB and Zhao CY: E2F is required for STAT3-mediated upregulation of cyclin B1 and Cdc2 expressions and contributes to G2-M phase transition. Acta Biochim Biophys Sin (Shanghai). 51:313–322. 2019.PubMed/NCBI View Article : Google Scholar
23	Pan XW, Chen L, Hong Y, Xu DF, Liu X, Li L, Huang Y, Cui LM, Gan SS, Yang QW, et al: Cui: EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling. Int J Oncol. 48:2580–2590. 2016.PubMed/NCBI View Article : Google Scholar
24	Lohberger B, Leithner A, Stuendl N, Kaltenegger H, Kullich W and Steinecker-Frohnwieser B: Diacerein retards cell growth of chondrosarcoma cells at the G2/M cell cycle checkpoint via cyclin B1/CDK1 and CDK2 downregulation. BMC Cancer. 15(891)2015.PubMed/NCBI View Article : Google Scholar
25	Ying Y, Wang Z, Tan Y, Cao H, Gao H, Zhang Z, Zeng S and Xu C: Identification and validation of immunohistochemical marker panels to predict the prognosis of muscle invasive bladder cancer. Transl Androl Urol. 12:176–186. 2023.PubMed/NCBI View Article : Google Scholar
26	Liu D, Xu W, Ding X, Yang Y, Su B and Fei K: Polymorphisms of CCNB1 associated with the clinical outcomes of platinum-based chemotherapy in Chinese NSCLC Patients. J Cancer. 8:3785–3794. 2017.PubMed/NCBI View Article : Google Scholar
27	Liu A, Zeng S, Lu X, Xiong Q, Xue Y, Tong L, Xu W, Sun Y, Zhang Z and Xu C: Overexpression of G2 and S phase-expressed-1 contributes to cell proliferation, migration, and invasion via regulating p53/FoxM1/CCNB1 pathway and predicts poor prognosis in bladder cancer. Int J Biol Macromol. 123:322–334. 2019.PubMed/NCBI View Article : Google Scholar
28	Chen Q, Hu J, Deng J, Fu B and Guo J: Bioinformatics analysis identified key molecular changes in bladder cancer development and recurrence. Biomed Res Int. 16(3917982)2019.PubMed/NCBI View Article : Google Scholar
29	Brcic L, Heidinger M, Sever AZ, Zacharias M, Jakopovic M, Fediuk M, Maier A, Quehenberger F, Seiwerth S and Popper H: Prognostic value of cyclin A2 and B1 expression in lung carcinoids. Pathology. 51:481–486. 2019.PubMed/NCBI View Article : Google Scholar