Association of RGS20 expression with the progression and prognosis of renal cell carcinoma

Jiang,Lin; Shen,Jiangwei; Zhang,Ning; He,Yongchao; Wan,Zhenghua

doi:10.3892/ol.2021.12904

Association of RGS20 expression with the progression and prognosis of renal cell carcinoma

Authors:
- Lin Jiang
- Jiangwei Shen
- Ning Zhang
- Yongchao He
- Zhenghua Wan
View Affiliations

Affiliations: Department of Urology, Caoxian People's Hospital, Heze, Shandong 274400, P.R. China, Department of Urology, The Fifth Hospital of Xiamen, Xiamen, Fujian 361101, P.R. China
Published online on: July 7, 2021 https://doi.org/10.3892/ol.2021.12904
Article Number: 643
Copyright: © Jiang 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

Regulator of G protein signaling 20 (RGS20) has been shown to be highly expressed in various types of cancer. The present study aimed to investigate the effects of RGS20 in patients with renal cell carcinoma (RCC) and in RCC cells. Bioinformatics analysis was performed to analyze the role of RGS20 in RCC. Quantitative PCR and western blotting were used to determine the mRNA and protein expression levels of RGS20 in cells, respectively. After RGS20 inhibition, the proliferation, apoptosis, migration and invasiveness of A‑498 cells were tested using MTT assay, EdU assay, propidium iodide staining, Annexin V‑FITC/PI kit, wound healing assay and Transwell assay. High RGS20 expression was closely associated with the progression and immune infiltration of RCC, and may be considered as an independent indicator of poor prognosis in RCC. After knocking down RGS20, the proliferation, migration and invasiveness of cells were impaired, the cell cycle was arrested at the G₀/G₁ phase, and the level of apoptosis was increased. In addition, the mRNA expression levels of securin, CDC20 and cyclin B1 were decreased in RGS20‑knockdown cells. RGS20 expression was significantly associated with the infiltration level of activated CD4 T cells, type 1 T helper cells and activated dendritic cells. In summary, RGS20 expression was associated with RCC progression and poor prognosis; thus, it may be used to estimate the prognosis of RCC and may serve as a new potential treatment strategy for RCC.

View Figures

View References

1	Khalil Ibrahim A: Trends of adult primary malignant renal tumors over 6 years. Pak J Med Sci. 29:1385–1388. 2013.PubMed/NCBI
2	Zhai W, Zhu R, Ma J, Gong D, Zhang H, Zhang J, Chen Y, Huang Y, Zheng J and Xue W: A positive feed-forward loop between LncRNA-URRCC and EGFL7/P-AKT/FOXO3 signaling promotes proliferation and metastasis of clear cell renal cell carcinoma. Mol Cancer. 18:812019. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
4	Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X and He J: Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 30:1–12. 2018. View Article : Google Scholar : PubMed/NCBI
5	Wong MCS, Goggins WB, Yip BHK, Fung FDH, Leung C, Fang Y, Wong SYS and Ng CF: Incidence and mortality of kidney cancer: Temporal patterns and global trends in 39 countries. Sci Rep. 7:156982017. View Article : Google Scholar : PubMed/NCBI
6	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
7	Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, et al: Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 375:2246–2254. 2016. View Article : Google Scholar : PubMed/NCBI
8	Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Leibovich BC and Zincke H: A multifactorial postoperative surveillance model for patients with surgically treated clear cell renal cell carcinoma. J Urol. 170:2225–2232. 2003. View Article : Google Scholar : PubMed/NCBI
9	Patard JJ, Kim HL, Lam JS, Dorey FJ, Pantuck AJ, Zisman A, Ficarra V, Han KR, Cindolo L, De La Taille A, et al: Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: An international multicenter study. J Clin Oncol. 22:3316–3322. 2004. View Article : Google Scholar : PubMed/NCBI
10	Sorbellini M, Kattan MW, Snyder ME, Reuter V, Motzer R, Goetzl M, McKiernan J and Russo P: A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol. 173:48–51. 2005. View Article : Google Scholar : PubMed/NCBI
11	Calvo E, Schmidinger M, Heng DY, Grünwald V and Escudier B: Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy. Cancer Treat Rev. 50:109–117. 2016. View Article : Google Scholar : PubMed/NCBI
12	Chen Z, Zhu R and Zheng J, Chen C, Huang C, Ma J, Xu C, Zhai W and Zheng J: Cryptotanshinone inhibits proliferation yet induces apoptosis by suppressing STAT3 signals in renal cell carcinoma. Oncotarget. 8:50023–50033. 2017. View Article : Google Scholar : PubMed/NCBI
13	Wang Y, Ho G, Zhang JJ, Nieuwenhuijsen B, Edris W, Chanda PK and Young KH: Regulator of G protein signaling Z1 (RGSZ1) interacts with Galpha i subunits and regulates Galpha i-mediated cell signaling. J Biol Chem. 277:48325–48332. 2002. View Article : Google Scholar : PubMed/NCBI
14	De Vries L, Elenko E, Hubler L, Jones TL and Farquhar MG: GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP-bound) form of G alpha i subunits. Proc Natl Acad Sci USA. 93:15203–15208. 1996. View Article : Google Scholar : PubMed/NCBI
15	Nunn C, Mao H, Chidiac P and Albert PR: RGS17/RGSZ2 and the RZ/A family of regulators of G-protein signaling. Semin Cell Dev Biol. 17:390–399. 2006. View Article : Google Scholar : PubMed/NCBI
16	Wang J, Ducret A, Tu Y, Kozasa T, Aebersold R and Ross EM: RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz gtpase-activating protein subfamily. J Biol Chem. 273:26014–26025. 1998. View Article : Google Scholar : PubMed/NCBI
17	Huang G, He X and Wei XL: lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR-365/RGS20 in oral squamous cell carcinoma. Oncol Rep. 39:1948–1956. 2018.PubMed/NCBI
18	Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, Xi Y, Howell P, Metge B, Samant RS, et al: The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics. 1:132008. View Article : Google Scholar : PubMed/NCBI
19	Li Q, Jin W, Cai Y, Yang F, Chen E, Ye D, Wang Q and Guan X: Regulator of G protein signaling 20 correlates with clinicopathological features and prognosis in triple-negative breast cancer. Biochem Biophys Res Commun. 485:693–697. 2017. View Article : Google Scholar : PubMed/NCBI
20	Li G, Wang M, Ren L, Li H, Liu Q, Ouyang Y, He L and Li F: Regulator of G protein signaling 20 promotes proliferation and migration in bladder cancer via NF-κB signaling. Biomed Pharmacother. 117:1091122019. View Article : Google Scholar : PubMed/NCBI
21	Yang L, Lee MM, Leung MM and Wong YH: Regulator of G protein signaling 20 enhances cancer cell aggregation, migration, invasion and adhesion. Cell Signal. 28:1663–1672. 2016. View Article : Google Scholar : PubMed/NCBI
22	Li J, Hu L, Liu Y, Huang L, Mu Y, Cai X and Weng C: DDX19A senses viral RNA and mediates NLRP3-dependent inflammasome activation. J Immunol. 195:5732–5749. 2015. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Yao X, Hu W, Zhang J, Huang C, Zhao H and Yao X: Application of cAMP-dependent catalytic subunit β (PRKACB) low expression in predicting worse overall survival: A potential therapeutic target for colorectal carcinoma. J Cancer. 11:4841–4850. 2020. View Article : Google Scholar : PubMed/NCBI
25	Subramanian A, Kuehn H, Gould J, Tamayo P and Mesirov JP: GSEA-P: A desktop application for gene set enrichment analysis. Bioinformatics. 23:3251–3253. 2007. View Article : Google Scholar : PubMed/NCBI
26	Chen H, Xu J, Hong J, Tang R, Zhang X and Fang JY: Long noncoding RNA profiles identify five distinct molecular subtypes of colorectal cancer with clinical relevance. Mol Oncol. 8:1393–1403. 2014. View Article : Google Scholar : PubMed/NCBI
27	Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, Zhong Y, Wu CJ, Sadanandam A, Hu B, et al: Yap1 activation enables bypass of oncogenic kras addiction in pancreatic cancer. Cell. 179:12392019. View Article : Google Scholar : PubMed/NCBI
28	Xu ZY, Zhao M, Chen W, Li K, Qin F, Xiang WW, Sun Y, Wei J, Yuan LQ, Li SK and Lin SH: Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma. PeerJ. 8:e95302020. View Article : Google Scholar : PubMed/NCBI
29	Yuan Q, Sun N, Zheng J, Wang Y, Yan X, Mai W, Liao Y and Chen X: Prognostic and immunological role of FUN14 domain containing 1 in pan-cancer: Friend or foe? Front Oncol. 9:15022020. View Article : Google Scholar : PubMed/NCBI
30	Hurst JH and Hooks SB: Regulator of G-protein signaling (RGS) proteins in cancer biology. Biochem Pharmacol. 78:1289–1297. 2009. View Article : Google Scholar : PubMed/NCBI
31	Hurst JH, Mendpara N and Hooks SB: Regulator of G-protein signalling expression and function in ovarian cancer cell lines. Cell Mol Biol Lett. 14:153–174. 2009. View Article : Google Scholar : PubMed/NCBI
32	James MA, Lu Y, Liu Y, Vikis HG and You M: RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway. Cancer Res. 69:2108–2116. 2009. View Article : Google Scholar : PubMed/NCBI
33	Wiechec E, Overgaard J and Hansen LL: A fragile site within the HPC1 region at 1q25.3 affecting RGS16, RGSL1, and RGSL2 in human breast carcinomas. Genes Chromosomes Cancer. 47:766–780. 2008. View Article : Google Scholar : PubMed/NCBI
34	Fang G, Yu H and Kirschner MW: The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev. 12:1871–1883. 1998. View Article : Google Scholar : PubMed/NCBI
35	Brown NR, Lowe ED, Petri E, Skamnaki V, Antrobus R and Johnson LN: Cyclin B and cyclin A confer different substrate recognition properties on CDK2. Cell Cycle. 6:1350–1359. 2007. View Article : Google Scholar : PubMed/NCBI
36	Zou H, McGarry TJ, Bernal T and Kirschner MW: Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science. 285:418–422. 1999. View Article : Google Scholar : PubMed/NCBI
37	Rajurkar M, Dang K, Fernandez-Barrena MG, Liu X, Fernandez-Zapico ME, Lewis BC and Mao J: IKBKE is required during KRAS-induced pancreatic tumorigenesis. Cancer Res. 77:320–329. 2017. View Article : Google Scholar : PubMed/NCBI
38	Yang W, Qu Y, Tan B, Jia Y, Wang N, Hu P and Wang J: Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma. Onco Targets Ther. 11:1305–1314. 2018. View Article : Google Scholar : PubMed/NCBI
39	Wang X, Teng F, Lu J, Mu D, Zhang J and Yu J: Expression and prognostic role of IKBKE and TBK1 in stage I non-small cell lung cancer. Cancer Manag Res. 11:6593–6602. 2019. View Article : Google Scholar : PubMed/NCBI