USP22 promotes proliferation in renal cell carcinoma by stabilizing survivin

Lin,Ying; Zhong,Hongbin; Sun,Baicheng; Peng,Yongtiao; Lu,Fuhua; Chen,Miaoxuan; Zhu,Maoshu; Huang,Jiyi

doi:10.3892/ol.2020.12108

USP22 promotes proliferation in renal cell carcinoma by stabilizing survivin

Authors:
- Ying Lin
- Hongbin Zhong
- Baicheng Sun
- Yongtiao Peng
- Fuhua Lu
- Miaoxuan Chen
- Maoshu Zhu
- Jiyi Huang
View Affiliations

Affiliations: Department of Nephrology, The Fifth Hospital of Xiamen, Xiamen, Fujian 361003, P.R. China, Central Laboratory, The Fifth Hospital of Xiamen, Xiamen, Fujian 361003, P.R. China
Published online on: September 15, 2020 https://doi.org/10.3892/ol.2020.12108
Article Number: 246

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

Renal cell carcinoma (RCC) is one of the commonest urological tumors. The incidence of RCC ranks third among urological tumors, after prostate cancer and bladder tumors. However, the etiology of RCC remains unclear. Ubiquitin‑specific protease 22 (USP22), a potential marker of cancer stem cells, is associated with the occurrence and progression of numerous tumors. However, the roles of USP22 in RCC have not yet been investigated. Survivin is a member of the inhibitor of apoptotic protein family involved in RCC progression. The present study first detected the expression of USP22 and survivin in RCC tissues using immunohistochemistry and western blotting. It was revealed that the protein levels of USP22 and survivin in RCC tissues were higher than those in adjacent normal renal tissue. Subsequently, it was demonstrated that USP22 knockdown inhibited the growth of an RCC cell line ACHN and downregulated the protein level of survivin, accompanied by an increased level of cleaved‑caspase‑3. By contrast, overexpression of USP22 promoted the growth of ACHN cells, upregulated the expression of survivin and decreased the level of cleaved‑caspase‑3. Notably, the changes in USP22 expression did not affect the SURVIVIN mRNA level. Finally, it was confirmed that USP22 interacted with survivin and stabilized it by downregulating its ubiquitination. The present results indicate that USP22 may regulate survivin via deubiquitination, thereby promoting the proliferation of RCC cells. The results of the current study suggest that USP22 may represent a novel therapeutic target for patients with RCC.

View Figures

View References

1	Barata PC and Rini BI: Treatment of renal cell carcinoma: Current status and future directions. CA Cancer J Clin. 67:507–524. 2017. View Article : Google Scholar : PubMed/NCBI
2	Capitanio U and Montorsi F: Renal cancer. Lancet. 387:894–906. 2016. View Article : Google Scholar : PubMed/NCBI
3	Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, et al: Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 380:1103–1115. 2019. View Article : Google Scholar : PubMed/NCBI
4	Dabestani S, Marconi L, Hofmann F, Stewart F, Lam TB, Canfield SE, Staehler M, Powles T, Ljungberg B and Bex A: Local treatments for metastases of renal cell carcinoma: A systematic review. Lancet Oncol. 15:e549–e561. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ricketts CJ and Linehan WM: Multi-regional sequencing elucidates the evolution of clear cell renal cell carcinoma. Cell. 173:540–542. 2018. View Article : Google Scholar : PubMed/NCBI
6	Yang X, Zang H, Luo Y, Wu J, Fang Z, Zhu W and Li Y: High expression of USP22 predicts poor prognosis and advanced clinicopathological features in solid tumors: A meta-analysis. Onco Targets Ther. 11:3035–3046. 2018. View Article : Google Scholar : PubMed/NCBI
7	Ao N, Wang L and Liu Y: Prognostic and clinicopathological significance of ubiquitin-specific protease 22 overexpression in cancers: Evidence from a meta-analysis. Onco Targets Ther. 10:5533–5540. 2017. View Article : Google Scholar : PubMed/NCBI
8	Melo-Cardenas J, Xu Y, Wei J, Tan C, Kong S, Gao B, Montauti E, Kirsammer G, Licht JD, Yu J, et al: USP22 deficiency leads to myeloid leukemia upon oncogenic Kras activation through a PU.1-dependent mechanism. Blood. 132:423–434. 2018. View Article : Google Scholar : PubMed/NCBI
9	Kim PJ, Plescia J, Clevers H, Fearon ER and Altieri DC: Survivin and molecular pathogenesis of colorectal cancer. Lancet. 362:205–209. 2003. View Article : Google Scholar : PubMed/NCBI
10	Arber C, Feng X, Abhyankar H, Romero E, Wu MF, Heslop HE, Barth P, Dotti G and Savoldo B: Survivin-specific T cell receptor targets tumor but not T cells. J Clin Invest. 125:157–168. 2015. View Article : Google Scholar : PubMed/NCBI
11	Campbell CS and Desai A: Tension sensing by Aurora B kinase is independent of survivin-based centromere localization. Nature. 497:118–121. 2013. View Article : Google Scholar : PubMed/NCBI
12	Saenz DT, Fiskus W, Manshouri T, Mill CP, Qian Y, Raina K, Rajapakshe K, Coarfa C, Soldi R, Bose P, et al: Targeting nuclear β-catenin as therapy for post-myeloproliferative neoplasm secondary AML. Leukemia. 33:1373–1386. 2019. View Article : Google Scholar : PubMed/NCBI
13	Krambeck AE, Dong H, Thompson RH, Kuntz SM, Lohse CM, Leibovich BC, Blute ML, Sebo TJ, Cheville JC, Parker AS and Kwon ED: Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma. Clin Cancer Res. 13:1749–1756. 2007. View Article : Google Scholar : PubMed/NCBI
14	Xiong C, Liu H, Chen Z, Yu Y and Liang C: Prognostic role of survivin in renal cell carcinoma: A system review and meta-analysis. Eur J Intern Med. 33:102–107. 2016. View Article : Google Scholar : PubMed/NCBI
15	Altieri DC: Survivin and apoptosis control. Adv Cancer Res. 88:31–52. 2003. View Article : Google Scholar : PubMed/NCBI
16	Vong QP, Cao K, Li HY, Iglesias PA and Zheng Y: Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 310:1499–1504. 2005. View Article : Google Scholar : PubMed/NCBI
17	Goldstein NS: The current state of renal cell carcinoma grading. Union internationale contre le cancer (UICC) and the American joint committee on cancer (AJCC). Cancer. 80:977–980. 1997. View Article : Google Scholar : PubMed/NCBI
18	Zeng F, Luo F, Lv S, Zhang H, Cao C, Chen X, Wang S, Li Z, Wang X, Dou X, et al: A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway. Anticancer Drugs. 25:663–672. 2014.PubMed/NCBI
19	Cikos S, Bukovska A and Koppel J: Relative quantification of mRNA: Comparison of methods currently used for real-time PCR data analysis. BMC Mol Biol. 8:1132007. View Article : Google Scholar : PubMed/NCBI
20	Tang B, Liang X, Tang F, Zhang J, Zeng S, Jin S, Zhou L, Kudo Y and Qi G: Expression of USP22 and survivin is an indicator of malignant behavior in hepatocellular carcinoma. Int J Oncol. 47:2208–2216. 2015. View Article : Google Scholar : PubMed/NCBI
21	Melo-Cardenas J, Zhang Y, Zhang DD and Fang D: Ubiquitin-specific peptidase 22 functions and its involvement in disease. Oncotarget. 7:44848–44856. 2016. View Article : Google Scholar : PubMed/NCBI
22	Ning J, Zhang J, Liu W, Lang Y, Xue Y and Xu S: Overexpression of ubiquitin-specific protease 22 predicts poor survival in patients with early-stage non-small cell lung cancer. Eur J Histochem. 56:e462012. View Article : Google Scholar : PubMed/NCBI
23	Liu T, Liu J, Chen Q, Jin S, Mi S, Shao W, Kudo Y, Zeng S and Qi G: Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma. Oncol Lett. 17:2040–2046. 2019.PubMed/NCBI
24	Melucci E, Cosimelli M, Carpanese L, Pizzi G, Izzo F, Fiore F, Golfieri R, Giampalma E, Sperduti I, Ercolani C, et al: Decrease of survivin, p53 and Bcl-2 expression in chemorefractory colorectal liver metastases may be predictive of radiosensivity radiosensivity after radioembolization with yttrium-90 resin microspheres. J Exp Clin Cancer Res. 32:132013. View Article : Google Scholar : PubMed/NCBI
25	Li G, Xie B, Li X, Chen Y, Wang Q, Xu Y, Xu-Welliver M and Zou L: Down-regulation of survivin and hypoxia-inducible factor-1 α by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft. Cancer Biother Radiopharm. 27:56–64. 2012. View Article : Google Scholar : PubMed/NCBI