RGS17 promotes the progression of kidney renal clear cell carcinoma via activating the cAMP signaling pathway

Ye Yanle; Huang Qi; Zhou Jin; Cai Jingshuang; Huang Zhiyang

doi:10.13406/j.cnki.cyxb.003626

您当前的位置：

首页 >

文章列表页 >

RGS17 promotes the progression of kidney renal clear cell carcinoma via activating the cAMP signaling pathway

Basic research | 更新时间：2025-10-23

- RGS17 promotes the progression of kidney renal clear cell carcinoma via activating the cAMP signaling pathway
- Journal of Chongqing Medical University Vol. 49, Issue 11, Pages: 1408-1418(2024)
- 作者机构：
  
  泉州市第一医院泌尿外科，泉州 352000
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003626
  CLC： R737.11
- Received：22 June 2024，
  
  Revised：2024-08-18，
  
  Accepted：22 August 2024，
  
  Published：28 November 2024
- 稿件说明：
移动端阅览
叶燕乐,黄琦,周金,等.RGS17通过激活cAMP信号通路促进肾透明细胞癌进展[J].重庆医科大学学报,2024,49(11):1408-1418.

Ye Yanle,Huang Qi,Zhou Jin,et al.RGS17 promotes the progression of kidney renal clear cell carcinoma via activating the cAMP signaling pathway[J].Journal of Chongqing Medical University,2024,49(11):1408-1418.
叶燕乐,黄琦,周金,等.RGS17通过激活cAMP信号通路促进肾透明细胞癌进展[J].重庆医科大学学报,2024,49(11):1408-1418. DOI： 10.13406/j.cnki.cyxb.003626.

Ye Yanle,Huang Qi,Zhou Jin,et al.RGS17 promotes the progression of kidney renal clear cell carcinoma via activating the cAMP signaling pathway[J].Journal of Chongqing Medical University,2024,49(11):1408-1418. DOI： 10.13406/j.cnki.cyxb.003626.

摘要

目的

探讨G蛋白信号蛋白家族的调节因子17（regulator of G protein signaling 17，RGS17）在肾透明细胞癌患者中的临床意义和功能机制。

方法

获得癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库中肾透明细胞癌（kidney renal clear cell carcinoma，KIRC）的RNAseq数据和相应的临床信息。利用R软件研究RGS17在KIRC中的表达差异及其与临床特征的关系。使用免疫组化及PCR进行验证。采用Kaplan-Meier（K-M）分析、受试者工作特征（receiver operating characteristic，ROC）曲线、单因素COX分析、多因素COX分析来评估患者的生存和预后，并构建nomogram模型。使用STRING进行RGS17相关基因的PPI网络构建，并进行 GO及KEGG富集分析。并采用 RT-qPCR、Western blot、CCK-8、Transwell 和划痕实验等方法检测RGS17对ACHN细胞增殖迁移及cAMP信号通路的影响。

结果

RGS17在KIRC中高表达，且RGS17的高表达与更高的T分期、临床分期、肿瘤转移显著相关。K-M生存分析显示，RGS17上调与KIRC患者总生存期、无疾病进展生存期下降密切相关。ROC曲线表明RGS17能较好的区分正常和KIRC患者，并在预测KIRC患者的预后方面具有一定的准确性。RGS17是KIRC独立预后因素。使用RGS17表达、临床分期、病理分级构建nomogram预后模型能较好预测1、3、5年生存率。RGS17敲低显著抑制ACHN细胞的增殖、迁移和侵袭能力。另外，RGS17敲低能够抑制cAMP信号通路的激活。

结论

RGS17在肾透明细胞癌中具有促癌基因的作用，其可能通过激活cAMP信号通路促进肾透明细胞癌的进展。

Abstract

Objective

To investigate the clinical significance and functional mechanism of regulator of G protein signaling 17 （RGS17） in patients with kidney renal clear cell carcinoma（KIRC）.

Methods

RNAseq data and related clinical information on KIRC were obtained from The Cancer Genome Atlas（TCGA） database. The differential expression of RGS17 in KIRC and its relationship with clinical characteristics were studied using R software. and the results were validated using immunohistochemistry and polymerase chain reaction（PCR）. Patient survival and outcome were analyzed by using the Kaplan-Meier（K-M） method，receiver operating characteristic（ROC） curve，and univariable and multivariable Cox analyses，and a nomogram model was constructed. We constructed the protein-protein interaction（PPI） network of RGS17-related genes using the STRING database，and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The effects of RGS17 on the proliferation and migration of ACHN cells and the cAMP signaling pathway were determined by real-time quantitative PCR，Western blot，Cell Counting Kit-8，transwell assay，and wound healing assay.

Results

RGS17 was highly expressed in KIRC，and its high expression was significantly associated with a higher T stage，a higher clinical stage，and tumor metastasis. The K-M survival analysis showed that RGS17 upregulation was closely related to decreased overall survival and progression-free survival in patients with KIRC. The ROC curve analysis indicated that RGS17 could well distinguish between normal people and patients with KIRC，showing certain accuracy in predicting the outcome of patients with KIRC. RGS17 was identified as an independent prognostic factor for KIRC. The nomogram model constructed using RGS17 expression，clinical stage，and pathological grade could well predict the 1-，3-，and 5-year survival rates. Knocking RGS17 down significantly suppressed the proliferation，migration，and invasion abilities of ACHN cells as well as the activation of the cAMP signaling pathway.

Conclusion

RGS17 acts as an oncogene in KIRC，which may promote the progression of KIRC by activating the cAMP signaling pathway.

关键词

Keywords

references

Gansler T ， Fedewa S ， Amin MB ， et al . Trends in reporting histological subtyping of renal cell carcinoma：association with cancer center type [J ] . Hum Pathol ， 2018 ， 74 ： 99 - 108 ．

Lu T ， Xu HR ， Dong W ， et al . Expression and prognosis analysis of PAQR5 in kidney cancer [J ] . Front Oncol ， 2022 ， 12 ： 955510 ．

Chow WH ， Dong LM ， Devesa SS . Epidemiology and risk factors for kidney cancer [J ] . Nat Rev Urol ， 2010 ， 7 （ 5 ）： 245 - 257 ．

Sethakorn N ， Dulin NO . RGS expression in cancer：oncomining the cancer microarray data [J ] . J Recept Signal Transduct Res ， 2013 ， 33 （ 3 ）： 166 - 171 ．

Yamauchi Y ， Miura Y ， Kanaho Y . Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs [J ] . Adv Biol Regul ， 2017 ， 63 ： 115 - 121 ．

Li YH ， Li LL ， Lin JY ， et al . Deregulation of RGS17 expression promotes breast cancer progression [J ] . J Cancer ， 2015 ， 6 （ 8 ）： 767 - 775 ．

Wang SC ， Zhang CC ， Chen RL . Circ_0006220 promotes non-small cell lung cancer progression via sponging miR-203-3p and regulating RGS17 expression [J ] . Hum Exp Toxicol ， 2022 ， 41 ： 9603271211062854 ．

Ma JH ， Wei HB ， Li XL ， et al . Hsa-miR-149-5p suppresses prostate carcinoma malignancy by suppressing RGS17 [J ] . Cancer Manag Res ， 2021 ， 13 ： 2773 - 2783 ．

Zhang W ， Qian S ， Yang GW ， et al . MicroRNA-199 suppresses cell proliferation，migration and invasion by downregulating RGS17 in hepatocellular carcinoma [J ] . Gene ， 2018 ， 659 ： 22 - 28 ．

Hooks SB ， Callihan P ， Altman MK ， et al . Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells [J ] . Mol Cancer ， 2010 ， 9 ： 289 ．

James MA ， Lu Y ， Liu Y ， et al . RGS17，an overexpressed gene in human lung and prostate cancer，induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway [J ] . Cancer Res ， 2009 ， 69 （ 5 ）： 2108 - 2116 ．

Li L ， Luo HS . G-protein signaling protein-17 （RGS17） is upregulated and promotes tumor growth and migration in human colorectal carcinoma [J ] . Oncol Res ， 2018 ， 26 （ 1 ）： 27 - 35 ．

Mancini M ， Righetto M ， Baggio G . Gender-related approach to kidney cancer management：moving forward [J ] . Int J Mol Sci ， 2020 ， 21 （ 9 ）： 3378 ．

Schulz S ， Woerl AC ， Jungmann F ， et al . Multimodal deep learning for prognosis prediction in renal cancer [J ] . Front Oncol ， 2021 ， 11 ： 788740 ．

Zheng BS ， Wang SD ， Zhang JY ， et al . Incidence，prognostic factors，and survival of patients with renal cancer：a population-based study [J ] . J Investig Surg ， 2023 ， 36 （ 1 ）： 2197506 ．

Hertz E ， Saarinen M ， Svenningsson P . GM1 is cytoprotective in GPR37-expressing cells and downregulates signaling [J ] . Int J Mol Sci ， 2021 ， 22 （ 23 ）： 12859 ．

Yin ZY ， Zhang XF ， Wang JZ ， et al . MoMip11，a MoRgs7-interacting protein，functions as a scaffolding protein to regulate cAMP signaling and pathogenicity in the rice blast fungus Magnaporthe oryzae [J ] . Environ Microbiol ， 2018 ， 20 （ 9 ）： 3168 - 3185 ．

Cabrera IE ， Oza Y ， Carrillo AJ ， et al . Regulator of G protein signaling proteins control growth，development and cellulase production in Neurospora crassa [J ] . J Fungi ， 2022 ， 8 （ 10 ）： 1076 ．

Zhang LS ， Ma HG ， Sun FH ， et al . MiR-203 inhibits the malignant behavior of prostate cancer cells by targeting RGS17 [J ] . Eur Rev Med Pharmacol Sci ， 2019 ， 23 （ 13 ）： 5667 - 5674 ．

Shikata Y ， Yoshimaru T ， Komatsu M ， et al . Protein kinase A inhibition facilitates the antitumor activity of xanthohumol，a valosin-containing protein inhibitor [J ] . Cancer Sci ， 2017 ， 108 （ 4 ）： 785 - 794 .

Zhang HY ， Kong QB ， Wang J ， et al . Complex roles of cAMP-PKA-CREB signaling in cancer [J ] . Exp Hematol Oncol ， 2020 ， 9 （ 1 ）： 32 .

Bitar MS ， Al-Mulla F . Upregulation of CREM/ICER suppresses wound endothelial CRE-HIF-1α-VEGF-dependent signaling and impairs angiogenesis in type 2 diabetes [J ] . Dis Model Mech ， 2015 ， 8 （ 1 ）： 65 - 80 ．

Jones C ， Bisserier M ， Bueno-Beti C ， et al . A novel secreted-cAMP pathway inhibits pulmonary hypertension via a feed-forward mechanism [J ] . Cardiovasc Res ， 2020 ， 116 （ 8 ）： 1500 - 1513 .

Hayes MP ， O’Brien JB ， Crawford RA ， et al . Fragment-based nuclear magnetic resonance screen against a regulator of G protein signaling identifies a binding “hot spot” [J ] . Chembiochem ， 2021 ， 22 （ 9 ）： 1609 - 1620 ．

Tie P ， Cheng J ， Xue MX ， et al . SLC18A3 promoted renal cancer development through acetylcholine/cAMP signaling [J ] . Am J Cancer Res ， 2022 ， 12 （ 9 ）： 4279 - 4289 ．

Zhang B ， Sun N ， Mu X ， et al . G protein alpha S subunit promotes cell proliferation of renal cell carcinoma with involvement of protein kinase A signaling [J ] . DNA Cell Biol ， 2017 ， 36 （ 3 ）： 237 - 242 ．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of matrix metalloproteinase 9 on the progression of osteosarcoma and its clinical significance

miR-335-5p inhibits the proliferation of gastric cancer cells by tagerting Oct4

Expression and clinical significance of KLF4 in the urine of patients with clear cell renal cell carcinoma

Effect of PLD2 gene silencing on proliferation and migration of colon cancer cells

Related Author

Luo Huimin

Pi Yubo

Chen Yanmeng

Wang Kai

Tang Ni

Huang Ailong

Hu Xiaobo

Cheng Anqi

Related Institution

Key Laboratory of Molecular Biology on Infectious Diseases，Ministry of Education，Chongqing Medical University

Department of Orthopaedics and Rehabilitation, Chongqing Traditional Chinese Medicine Hospital

Department of Gastrointestinal Surgery，The First Affiliated Hospital of Chongqing Medical University

Department of Urology，People’s Hospital in Bishan District

Department of Integrated Traditional and Western Medicine,The First Affiliated Hospital of Chongqing Medical University

⁰