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Published in: Irish Journal of Medical Science (1971 -) 4/2022

31-08-2021 | Kidney Cancer | Original Article

UBA2 promotes the progression of renal cell carcinoma by suppressing the p53 signaling

Authors: Xinbo Du, Jianguo Shi

Published in: Irish Journal of Medical Science (1971 -) | Issue 4/2022

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Abstract

Background

Renal cell carcinoma or RCC is a type of malignancy commonly occurred in the human kidney especially in the adults. The pathogenesis of RCC involves the complex networking of multiple signaling pathways, and the underlying molecular mechanisms remain largely unclear.

Objectives

This study aimed to elucidate the regulatory functions of UBA2 and explore its potential downstream molecules during the tumor progression in RCC.

Methods

In this paper, the expression of UBA2 and associated molecules was examined by RT-qPCR and western blotting. The proliferative activity of RCC cells was determined using CCK-8 assay and immunofluorescence staining of proliferation-related marker Ki-67. Moreover, the cell distribution and apoptosis were evaluated by flow cytometry.

Results

Our results revealed the upregulation of UBA2 in RCC tissues and cells, and the high-expression of UBA2 was also associated with bigger tumor size, more advanced stage, and poorer overall survival in RCC patients. In addition, UBA2 knockdown was able to suppress the growth of RCC cells and induced cell cycle arrest at G0/G1 phase. Furthermore, the p53 signaling could be the novel target of UBA2 in RCC, and UBA2 affected the biological behaviors of RCC cells in a p53-dependent manner.

Conclusion

In summary, UBA2 was able to enhance the proliferation, inhibit the apoptosis, and suppress cell cycle arrest in RCC cells by targeting the p53 pathway.
Literature
1.
go back to reference Nabi S, Kessler E, Bernard B et al (2018) Renal cell carcinoma: a Rev Biol Pathophysiol F1000Res 7:307 Nabi S, Kessler E, Bernard B et al (2018) Renal cell carcinoma: a Rev Biol Pathophysiol F1000Res 7:307
2.
go back to reference Sheth S, Scatarige JC, Horton KM et al (2001) Current concepts in the diagnosis and management of renal cell carcinoma: role of multidetector ct and three-dimensional CT. Radiographics 21:S237–S254CrossRef Sheth S, Scatarige JC, Horton KM et al (2001) Current concepts in the diagnosis and management of renal cell carcinoma: role of multidetector ct and three-dimensional CT. Radiographics 21:S237–S254CrossRef
3.
go back to reference Vera-Badillo FE, Conde E, Duran I (2012) Chromophobe renal cell carcinoma: a review of an uncommon entity. Int J Urol 19:894–900CrossRef Vera-Badillo FE, Conde E, Duran I (2012) Chromophobe renal cell carcinoma: a review of an uncommon entity. Int J Urol 19:894–900CrossRef
4.
go back to reference Gray R, Harris G (2019) Renal cell carcinoma: diagnosis and management. Am Fam Physician 99(3):179–184PubMed Gray R, Harris G (2019) Renal cell carcinoma: diagnosis and management. Am Fam Physician 99(3):179–184PubMed
5.
go back to reference Chappell WH, Steelman LS, Long JM et al (2011) Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget 2:135–165CrossRef Chappell WH, Steelman LS, Long JM et al (2011) Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget 2:135–165CrossRef
6.
go back to reference Von Schulz-Hausmann S, Schmeel L, Schmeel F, Schmidt-Wolf I (2014) Targeting the Wnt/beta-catenin pathway in renal cell carcinoma. Anticancer Res 34(8):4101–4108 Von Schulz-Hausmann S, Schmeel L, Schmeel F, Schmidt-Wolf I (2014) Targeting the Wnt/beta-catenin pathway in renal cell carcinoma. Anticancer Res 34(8):4101–4108
7.
go back to reference Shang D, Liu Y, Ito N et al (2007) Defective Jak- Stat activation in renal cell carcinoma is associated with interferon-alpha resistance. Cancer Sci 98:1259–1264CrossRef Shang D, Liu Y, Ito N et al (2007) Defective Jak- Stat activation in renal cell carcinoma is associated with interferon-alpha resistance. Cancer Sci 98:1259–1264CrossRef
8.
9.
go back to reference Flotho A, Melchior F (2013) Sumoylation: a regulatory protein modification in health and disease. Annu Rev Biochem 82:357–385CrossRef Flotho A, Melchior F (2013) Sumoylation: a regulatory protein modification in health and disease. Annu Rev Biochem 82:357–385CrossRef
10.
go back to reference Andreou A, Tavernarakis N (2009) SUMOylation and cell signalling. Biotechnol J 4(12):1740–1752CrossRef Andreou A, Tavernarakis N (2009) SUMOylation and cell signalling. Biotechnol J 4(12):1740–1752CrossRef
11.
go back to reference Geiss-Friedlander R, Melchior F (2007) Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol 8(12):947–956CrossRef Geiss-Friedlander R, Melchior F (2007) Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol 8(12):947–956CrossRef
12.
13.
go back to reference Schneeweis C, Hassan Z, Schick M et al (2021) The SUMO pathway in pancreatic cancer: insights and inhibition. Br J Cancer 124:531–538CrossRef Schneeweis C, Hassan Z, Schick M et al (2021) The SUMO pathway in pancreatic cancer: insights and inhibition. Br J Cancer 124:531–538CrossRef
14.
go back to reference Schmidt D, Muller S (2002) Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity. Proc Natl Acad Sci USA 99(5):2872–2877CrossRef Schmidt D, Muller S (2002) Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity. Proc Natl Acad Sci USA 99(5):2872–2877CrossRef
15.
go back to reference Mantovani F, Collavin L, Del Sal G (2019) Mutant p53 as a guardian of the cancer cell. Cell Death Differ 26:199–212CrossRef Mantovani F, Collavin L, Del Sal G (2019) Mutant p53 as a guardian of the cancer cell. Cell Death Differ 26:199–212CrossRef
16.
go back to reference Ozaki T, Nakagawara A (2011) Role of p53 in cell death and human cancer. Cancers (Basel) 3(1):994–1013CrossRef Ozaki T, Nakagawara A (2011) Role of p53 in cell death and human cancer. Cancers (Basel) 3(1):994–1013CrossRef
17.
go back to reference Chen J (2016) The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Sping Harb Perspect Med 6(3):a026104 Chen J (2016) The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Sping Harb Perspect Med 6(3):a026104
18.
go back to reference Wu S, Chiang C (2009) P53 sumoylation: mechanistic insights from reconstitution studies. Epigenetics 4(7):445–451CrossRef Wu S, Chiang C (2009) P53 sumoylation: mechanistic insights from reconstitution studies. Epigenetics 4(7):445–451CrossRef
19.
go back to reference He X, Riceberg J, Soucy T et al (2017) Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nat Chem Biol 13:1164–1171CrossRef He X, Riceberg J, Soucy T et al (2017) Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nat Chem Biol 13:1164–1171CrossRef
20.
go back to reference Perri F, Pisconti S, Scarpati G (2016) P53 mutations and cancer: a tight linkage. Ann Transl Med 4(24):522CrossRef Perri F, Pisconti S, Scarpati G (2016) P53 mutations and cancer: a tight linkage. Ann Transl Med 4(24):522CrossRef
21.
go back to reference Lozano G (2019) Restoring p53 in cancer: the promises and the challenges. J Mol Cell Biol 11(7):615–619CrossRef Lozano G (2019) Restoring p53 in cancer: the promises and the challenges. J Mol Cell Biol 11(7):615–619CrossRef
22.
go back to reference Bertheau P, Espie M, Turpin E et al (2008) TP53 status and response to chemotherapy in breast cancer. Pahtobiology 75:132–139 Bertheau P, Espie M, Turpin E et al (2008) TP53 status and response to chemotherapy in breast cancer. Pahtobiology 75:132–139
23.
go back to reference Gong L, Qi R, Li D (2017) Sumoylation pathway as potential therapeutic targets in cancer. Curr Mol Med 16(10):900–905CrossRef Gong L, Qi R, Li D (2017) Sumoylation pathway as potential therapeutic targets in cancer. Curr Mol Med 16(10):900–905CrossRef
Metadata
Title
UBA2 promotes the progression of renal cell carcinoma by suppressing the p53 signaling
Authors
Xinbo Du
Jianguo Shi
Publication date
31-08-2021
Publisher
Springer International Publishing
Published in
Irish Journal of Medical Science (1971 -) / Issue 4/2022
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-021-02763-4

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