Rgs20, short for Regulator of G protein signaling 20, is a member of the RGS protein superfamily. RGS proteins act as key negative regulators of G protein-mediated signal transduction, and Rgs20, through its GTPase accelerating protein (GAP) activity, deactivates α-subunits of heterotrimeric G proteins. It can also act through non-GAP related functions and is involved in regulating Gαz and Gi/o-mediated signaling [4]. Palmitoylation, an important post-translational modification, is a regulatory mechanism controlling Rgs20 function [4].

In multiple cancers, Rgs20 has been found to play oncogenic roles. In penile cancer, high Rgs20 expression is associated with tumor stage, nodal status, and pelvic metastasis. It promotes tumor progression by modulating PI3K/AKT signaling activation [2]. In non-small cell lung carcinoma, higher Rgs20 expression is correlated with a poorer five-year survival rate, and it drives cell proliferation by triggering autophagy via the inhibition of PKA-Hippo signaling [3]. In renal cell carcinoma, high Rgs20 expression is closely associated with the progression and immune infiltration, and knockdown of Rgs20 impairs cell proliferation, migration, and invasiveness [5]. In hepatocellular carcinoma, miR-204-5p inhibits the disease by targeting and downregulating Rgs20 expression [6]. In triple-negative breast cancer, Rgs20 is upregulated in lymph node-positive cases, and high expression is associated with lymph node metastasis and poor relapse-free survival [7]. In oral squamous cell carcinoma, lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR-365/Rgs20 axis [8]. Also, in lung adenocarcinoma, the transcription factor SP1 activates Rgs20 expression through super-enhancers to promote cancer progression [1].

In conclusion, Rgs20 is an important regulator in G protein-mediated signal transduction. Its abnormal expression is closely associated with the progression and prognosis of multiple cancers, including penile, lung, renal, hepatocellular, triple-negative breast, and oral squamous cell carcinomas. These findings from in vivo and in vitro studies provide insights into Rgs20's role in cancer biology, suggesting it could be a potential target for cancer therapies.

References:

1. Shan, Liying, Wang, Wenmeng, Du, Lijuan, Sui, Guangchao, Liu, Fang. 2024. SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2401834121. doi:10.1073/pnas.2401834121. https://pubmed.ncbi.nlm.nih.gov/38976739/

2. Shi, Dazun, Tong, Shiyu, Han, Hui, Hu, Xiheng. 2022. RGS20 Promotes Tumor Progression through Modulating PI3K/AKT Signaling Activation in Penile Cancer. In Journal of oncology, 2022, 1293622. doi:10.1155/2022/1293622. https://pubmed.ncbi.nlm.nih.gov/35498542/

3. Ding, Xiaoyan, Li, Xiaoxia, Jiang, Yanxia, Li, Bing, Zhao, Robert Chunhua. 2024. RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway. In Cancer cell international, 24, 93. doi:10.1186/s12935-024-03282-9. https://pubmed.ncbi.nlm.nih.gov/38431606/

4. Zhang, Qian, Sjögren, Benita. 2023. Palmitoylation of RGS20 affects Gαo-mediated signaling independent of its GAP activity. In Cellular signalling, 107, 110682. doi:10.1016/j.cellsig.2023.110682. https://pubmed.ncbi.nlm.nih.gov/37075876/

5. Jiang, Lin, Shen, Jiangwei, Zhang, Ning, He, Yongchao, Wan, Zhenghua. 2021. Association of RGS20 expression with the progression and prognosis of renal cell carcinoma. In Oncology letters, 22, 643. doi:10.3892/ol.2021.12904. https://pubmed.ncbi.nlm.nih.gov/34386065/

6. Su, Yanqing, Lu, Yao, An, Honglin, Huang, Bin, Lin, Jiumao. 2023. MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20. In ACS pharmacology & translational science, 6, 1817-1828. doi:10.1021/acsptsci.3c00114. https://pubmed.ncbi.nlm.nih.gov/38093845/

7. Li, Quan, Jin, Wenxu, Cai, Yefeng, Wang, Qingxuan, Guan, Xiaoxiang. 2017. Regulator of G protein signaling 20 correlates with clinicopathological features and prognosis in triple-negative breast cancer. In Biochemical and biophysical research communications, 485, 693-697. doi:10.1016/j.bbrc.2017.02.106. https://pubmed.ncbi.nlm.nih.gov/28237701/

8. Huang, Gang, He, Xin, Wei, Xin-Li. 2018. lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma. In Oncology reports, 39, 1948-1956. doi:10.3892/or.2018.6283. https://pubmed.ncbi.nlm.nih.gov/29484420/