Rgs17, also known as RGSZ2, is a member of the RZ/A subfamily of regulators of G-protein signaling (RGS proteins) [1,5]. RGS proteins act as GTPase-activating proteins (GAPs), turning off G-proteins and negatively regulating G-protein coupled receptor (GPCR) signaling. Rgs17 specifically inhibits receptor signaling via G(i/o), G(z), and G(q) over G(s), enhancing cAMP-dependent signaling and inhibiting calcium signaling [5]. It has a simple structure with a conserved amino-terminal cysteine string motif, RGS box, and short carboxyl-terminal, which confer GAP activity and the ability to interact with other proteins [1].

In nasopharyngeal carcinoma (NPC), Rgs17 overexpression significantly reduces cell proliferation, decreases mitochondrial membrane potential, and induces apoptosis. It also improves the sensitivity of NPC cells to 5-fluorouracil (5-FU) [2]. In prostate carcinoma, miR-149-5p suppresses tumor malignancy by targeting and inhibiting Rgs17, as Rgs17 acts as an oncogene in this context [3]. In abdominal aortic aneurysm (AAA), circ_0000285 promotes the development of AAA by regulating the miR-599/Rgs17 network, with Rgs17 overexpression suppressing vascular smooth muscle cell (VSMC) proliferation and stimulating apoptosis [4]. In breast cancer, Rgs17 expression is up-regulated, enhancing cell migration, invasion, and proliferation, and it is a direct target of miR-32 [6]. In non-small cell lung cancer (NSCLC), circ_0006220 promotes NSCLC development by up-regulating Rgs17 expression through sponging miR-203-3p [7]. In cisplatin-induced ototoxicity, Rgs17 knockout in hair cells protects against cisplatin-induced elevation of auditory brainstem response (ABR) thresholds, outer hair cell loss, cochlear inflammation, and inner hair cell synaptopathy, suggesting Rgs17 is implicated in cisplatin ototoxicity [8].

In conclusion, Rgs17 plays diverse and significant roles in multiple biological processes and disease conditions. Its function as a regulator of G-protein signaling impacts various cellular activities. The use of gene knockout models, such as in the study of cisplatin ototoxicity, has revealed its role in disease-related processes, highlighting its potential as a therapeutic target for diseases like NPC, prostate carcinoma, AAA, breast cancer, NSCLC, and cisplatin-induced ototoxicity.

References:

1. Nunn, Caroline, Mao, Helen, Chidiac, Peter, Albert, Paul R. 2006. RGS17/RGSZ2 and the RZ/A family of regulators of G-protein signaling. In Seminars in cell & developmental biology, 17, 390-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16765607/

2. Yu, Qianqian, Zhang, Niankai, Jiang, Yan, Li, Na, Guan, Ge. 2018. RGS17 inhibits tumorigenesis and improves 5-fluorouracil sensitivity in nasopharyngeal carcinoma. In OncoTargets and therapy, 11, 7591-7600. doi:10.2147/OTT.S176002. https://pubmed.ncbi.nlm.nih.gov/30464507/

3. Ma, Jinhua, Wei, Hongbing, Li, Xianlin, Qu, Xi. 2021. Hsa-miR-149-5p Suppresses Prostate Carcinoma Malignancy by Suppressing RGS17. In Cancer management and research, 13, 2773-2783. doi:10.2147/CMAR.S281968. https://pubmed.ncbi.nlm.nih.gov/33790651/

4. Ren, Junwen, Fang, Chao, Liu, Ying, Xie, Peilin. . Hsa_circ_0000285-Mediated miR-599/RGS17 Axis Participates in the Pathogenesis of Abdominal Aortic Aneurysm by Regulating the Functions of Vascular Smooth Muscle Cells. In Annals of clinical and laboratory science, 53, 238-247. doi:. https://pubmed.ncbi.nlm.nih.gov/37094862/

5. Mao, Helen, Zhao, Qingshi, Daigle, Mireille, Chidiac, Peter, Albert, Paul R. 2004. RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling. In The Journal of biological chemistry, 279, 26314-22. doi:. https://pubmed.ncbi.nlm.nih.gov/15096504/

6. Li, Yuhua, Li, Liliang, Lin, Junyi, Xie, Jianhui, Zhao, Ziqin. 2015. Deregulation of RGS17 Expression Promotes Breast Cancer Progression. In Journal of Cancer, 6, 767-75. doi:10.7150/jca.11833. https://pubmed.ncbi.nlm.nih.gov/26185539/

7. Wang, Shaochun, Zhang, Chengcheng, Chen, Ruilin. . Circ_0006220 promotes non-small cell lung cancer progression via sponging miR-203-3p and regulating RGS17 expression. In Human & experimental toxicology, 41, 9603271211062854. doi:10.1177/09603271211062854. https://pubmed.ncbi.nlm.nih.gov/35041543/

8. Al Aameri, Raheem F H, Alanisi, Entkhab M A, Al Sallami, Dheyaa, Rybak, Leonard P, Ramkumar, Vickram. 2025. Role of RGS17 in cisplatin-induced cochlear inflammation and ototoxicity via caspase-3 activation. In Frontiers in immunology, 16, 1470625. doi:10.3389/fimmu.2025.1470625. https://pubmed.ncbi.nlm.nih.gov/40061942/