Zhang Lixia, Yang Weibing, Yang Jin, Sun Fu
Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, Shaanxi 710061, China.
Department of Oncology, Xi'an Daxing Hospital, Xi'an, Shaanxi 710016, China.
J Clin Biochem Nutr. 2023 Jul;73(1):43-51. doi: 10.3164/jcbn.22-125. Epub 2023 Jul 1.
The G protein-coupled receptor, class C, group 5, member A (GPRC5A) plays a key role in various diseases, but its effect on hepatocellular carcinoma (HCC) and the potential underlying mechanisms remains unclear. In the present study, we explored the effect of GPRC5A on the progression of HCC and further explored its mechanism of action. The results revealed that the expression of GPRC5A was lower in HCC tissues and cells. Overexpression of GPRC5A suppressed the proliferation and epithelial-mesenchymal transition (EMT) of HCC cells. In addition, overexpression of GPRC5A induced oxidative stress and apoptosis. Further study showed that overexpression of GPRC5A inhibited the expression of STAT3/Socs3/c-MYC related-protein and the NLRP3 inflammasome. Moreover, the STAT3/Socs3/c-MYC and NLRP3 inflammasome was involved in the effect of GPRC5A on HCC cells. These results suggest that GPRC5A suppresses proliferation and EMT, induces oxidative stress and leads to apoptosis of HCC cells, potentially by regulating STAT3/Socs3/c-MYC signalling and the NLRP3 inflammasome. These findings suggest that GPRC5A has an anti-tumor effect in the formation of HCC, and the molecular therapy of GPRC5A provides a theoretical basis for treating HCC.
G蛋白偶联受体C类第5组成员A（GPRC5A）在多种疾病中起关键作用，但其对肝细胞癌（HCC）的影响及潜在机制尚不清楚。在本研究中，我们探讨了GPRC5A对HCC进展的影响，并进一步探究其作用机制。结果显示，GPRC5A在HCC组织和细胞中的表达较低。GPRC5A的过表达抑制了HCC细胞的增殖和上皮-间质转化（EMT）。此外，GPRC5A的过表达诱导了氧化应激和细胞凋亡。进一步研究表明，GPRC5A的过表达抑制了STAT3/Socs3/c-MYC相关蛋白和NLRP3炎性小体的表达。而且，STAT3/Socs3/c-MYC和NLRP3炎性小体参与了GPRC5A对HCC细胞的作用。这些结果表明，GPRC5A可能通过调节STAT3/Socs3/c-MYC信号通路和NLRP3炎性小体来抑制HCC细胞的增殖和EMT，诱导氧化应激并导致细胞凋亡。这些发现提示GPRC5A在HCC形成过程中具有抗肿瘤作用，GPRC5A的分子治疗为HCC的治疗提供了理论依据。
