Regulator of G protein signaling-1 regulates immune infiltration and macrophage polarization in clear cell renal cell carcinoma

• Published in: International urology and nephrology 2024-02, Vol.56 (2), p.451-466
• Main Authors: Liu, Kun, Xia, Dian, Bian, Hege, Peng, Longfei, Dai, Shuxin, Liu, Chang, Jiang, Chao, Wang, Yi, Jin, Juan, Bi, Liangkuan
• Format: Article
• Language: English
• Subjects: Apoptosis; Bioinformatics; Carcinoma, Renal Cell - genetics; Cell culture; Clear cell-type renal cell carcinoma; GTP-Binding Proteins; Humans; Infiltration; Kidney cancer; Kidney Neoplasms - genetics; Leukocyte migration; Macrophages; Medicine; Medicine & Public Health; Metastases; Nephrology; Patients; Polarization; Proteins; Signal Transduction; Therapeutic targets; Tumor Microenvironment; Tumors; Urology; Urology - Original Paper
• ISSN: 1573-2584; 0301-1623; 1573-2584
• DOI: 10.1007/s11255-023-03794-9

Objective To better understand how to clear cell renal cell cancer (ccRCC) is affected by the regulator of G protein signaling-1 (RGS1), its effect on immune infiltration, macrophage polarization, tumor proliferation migration, and to explore whether RGS1 may serve as a marker and therapeutic target for ccRCC. Patients and methods In this study, a total of 20 surgical specimens of patients with pathological diagnosis of ccRCC admitted to the Department of Urology of the Second Affiliated Hospital of Anhui Medical University from November 2021 to June 2022 were selected for pathological and protein testing, while the expression of RGS1 in tumors, immune infiltration, and macrophage polarization, particularly M2 macrophage linked to the development of tumor microenvironment (TME), were combined with TGCA database and GO analysis. We also further explored and studied the expression and function of RGS1 in TME, investigated how RGS1 affected tumor growth, migration, apoptosis, and other traits, and initially explored the signaling pathways and mechanisms that RGS1 may affect. Results RGS1 was found to be expressed at higher quantities in ccRCC than in normal cells or tissues, according to bioinformatics analysis and preliminary experimental data from this work. Using the TCGA database and GO analysis to describe the expression of RGS1 in a range of tumors, it was found that ccRCC had a much higher level of RGS1 expression than other tumor types. The results of gene enrichment analysis indicated that overexpression of RGS1 may be associated with immune infiltration. The outcomes of in vitro tests revealed that RGS1 overexpression in ccRCC did not significantly alter the proliferation and migration ability of ccRCC, but RGS1 overexpression promoted apoptosis in ccRCC. By in vitro co-culture experiments, RGS1 overexpression inhibited M2 macrophage polarization and also suppressed the Jagged-1/Notch signaling pathway. Conclusions RGS1 is highly expressed in ccRCC, while overexpression of RGS1 may increase immune infiltration in the TME and reduce the polarization of M2 macrophages while promoting apoptosis in ccRCC.