Rgs20, also known as Regulator of G protein signaling 20, is a member of the RGS protein superfamily. It serves as a key negative regulator of G protein-mediated signal transduction, mainly through its GTPase accelerating protein (GAP) activity to deactivate α-subunits of heterotrimeric G proteins [3]. It has been associated with multiple signaling pathways, such as the PI3K/AKT, PKA-Hippo signaling pathways, and is involved in important cellular functions like cell proliferation, migration, and apoptosis, with significant implications in cancer biology [1,2]. Genetic models are valuable for studying Rgs20 to better understand its function in normal and disease states.

In penile cancer, knockdown of Rgs20 attenuated cell viability, BrdU incorporation, soft agar clonogenesis, caspase-3 activity, and cell migration/invasion, and it regulated PI3K/AKT signaling activation [1]. In non-small cell lung carcinoma, Rgs20 overexpression increased cell proliferation by activating autophagy and inhibiting the PKA-Hippo signaling pathway, and Rgs20 knockdown had the opposite effect [2]. In renal cell carcinoma, knocking down Rgs20 impaired cell proliferation, migration, and invasiveness, arrested the cell cycle at the G0/G1 phase, and increased apoptosis [4]. In hepatocellular carcinoma, miR-204-5p inhibited the progression of HCC by targeting and downregulating Rgs20 expression [5]. In oral squamous cell carcinoma, knockdown of lncRNA NEAT1, which regulates Rgs20 through miR-365, inhibited cell proliferation and invasion [6].

In conclusion, Rgs20 plays crucial roles in various cancer-related biological processes, including cell proliferation, apoptosis, migration, and invasion, mainly through its regulation of multiple signaling pathways. Studies using gene-knockdown models in different cancer types have revealed its significance in cancer progression, highlighting its potential as a diagnostic, prognostic marker, and a therapeutic target in cancer treatment.