Shi Dazun, Tong Shiyu, Han Hui, Hu Xiheng
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, China.
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
J Oncol. 2022 Apr 19;2022:1293622. doi: 10.1155/2022/1293622. eCollection 2022.
Regulator of G protein signaling 20 (RGS20) plays an important role in regulating neuronal G protein-coupled receptor signaling; however, its expression and oncogenic function in penile cancer (PC) remains unclear. Here, we observed high RGS20 expression in PC tissues compared to normal/adjacent penile tissues, which was closely associated with tumor stage, nodal status, and pelvic metastasis in our PC cohort. The cellular functional analysis of RGS20 revealed that manipulation of the RGS20 expression markedly affected cell viability, BrdU incorporation, soft agar clonogenesis, caspase-3 activity, and cell migration/invasion in PC cell models. Moreover, RGS20 could interact with PI3K p85 subunit and regulate PI3K/AKT signaling activation in PC cell lines. Knockdown of the PI3K p85 or p110 subunit attenuated cell viability, BrdU incorporation, soft agar clonogenesis, and cell migration/invasion in PC cell lines. In contrast, the overexpression of constitutively activated PI3K p110 mutant restored cell proliferation and cell migration/invasion caused by RGS20 depletion in PC cells. Consistent with the in vitro findings, RGS20 depletion attenuated PI3K/AKT signaling activation and suppressed tumor growth in a murine xenograft model. Importantly, the high RGS20 expression was associated with PI3K/AKT signaling activation and unfavorable progression-free/overall survival, highlighting the clinical relevance of RGS20/PI3K/AKT signaling in PC. In conclusion, the aberrant RGS20 expression may serve as a diagnostic and prognostic marker for PC. RGS20 may promote PC progression through modulating PI3K/AKT signaling activation, which may assist with the development of RGS20-targeting therapeutics in the future.
G蛋白信号调节因子20（RGS20）在调节神经元G蛋白偶联受体信号传导中起重要作用；然而，其在阴茎癌（PC）中的表达和致癌功能仍不清楚。在这里，我们观察到与正常/相邻阴茎组织相比，PC组织中RGS20表达较高，这与我们PC队列中的肿瘤分期、淋巴结状态和盆腔转移密切相关。RGS20的细胞功能分析表明，在PC细胞模型中，RGS20表达的操纵显著影响细胞活力、BrdU掺入、软琼脂克隆形成、caspase-3活性以及细胞迁移/侵袭。此外，RGS20可与PI3K p85亚基相互作用并调节PC细胞系中的PI3K/AKT信号激活。敲低PI3K p85或p110亚基可减弱PC细胞系中的细胞活力、BrdU掺入、软琼脂克隆形成以及细胞迁移/侵袭。相反，组成型激活的PI3K p110突变体的过表达恢复了PC细胞中RGS20缺失引起的细胞增殖和细胞迁移/侵袭。与体外研究结果一致，RGS20缺失减弱了PI3K/AKT信号激活并抑制了小鼠异种移植模型中的肿瘤生长。重要的是，高RGS20表达与PI3K/AKT信号激活以及无进展/总生存期不良相关，突出了RGS20/PI3K/AKT信号在PC中的临床相关性。总之，异常的RGS20表达可能作为PC的诊断和预后标志物。RGS20可能通过调节PI3K/AKT信号激活促进PC进展，这可能有助于未来开发靶向RGS20的治疗方法。
