Alausa Abdullahi, Victor Ugwu Chukwuebuka, Fadahunsi Olumide Samuel, Owolabi Nurudeen, Adeniji Adeolu, Olatinwo Mercy, Ogunlana Abdeen Tunde, Olaleke Barakat, Balogun Toheeb Adewale, Ogundepo Sunday, Adegbola Peter Ifeoluwa
Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyostate, Nigeria.
Department of Biochemistry, University of Nigeria, Nsukka, Nigeria.
Pharmacol Res. 2022 Jun;180:106242. doi: 10.1016/j.phrs.2022.106242. Epub 2022 May 2.
Cancer progression is enhanced through cell proliferation, with the crucial role of the transducer and transmembrane -signal regulator (GNG12) bringing it to the fore. Dysregulation of cancer cell metabolism, evasion of the immune system, cell cycle, apoptosis, and chemoresistance result from inconsistent initiation of the NF-kB signaling pathway. We excerpt from previous studies that overactivation of the canonic NF-kB cascade occurs in varieties of tumor cells, which results in the growth of lymphovascular invasion, as well as neural invasion. Recently, research has adduced that a particular G protein- coupled receptor (GNG12) is silently involved in the activation of the NF-kB signal, which supports the evasion of cancer immunity and in turn activates cancer proliferation, angiogenesis, and immunotherapeutic resistance. While the likely impact of GNG12 in relation to the progression of tumors is being established, there is insufficient knowledge regarding the functions and mechanisms of GNG12 in cancer immunity. Furthermore, the cancer-associated role as well as the clinical correlation of GNG12 have long been unknown; thus, their identification is more likely to pave the path for a novel regime of tumor suppression. In this study, we established the silent role of GNG12 in activating NF-kB genes and the synergism between NF-kB and PD-L1 expression. Captivatingly, we reported that silencing GNG12 gene downregulates the transcription of PD-L1 gene. We therefore suggested that GNG12 is a risk factor for several cancers, and a possible target for immunotherapy.
细胞增殖促进癌症进展，其中转导器和跨膜信号调节因子（GNG12）发挥关键作用，使其备受关注。NF-κB信号通路起始不一致导致癌细胞代谢失调、逃避免疫系统、细胞周期紊乱、凋亡异常以及产生化疗耐药性。我们从以往研究中得知，经典NF-κB级联反应在多种肿瘤细胞中过度激活，导致淋巴血管浸润以及神经浸润生长。最近，研究表明一种特定的G蛋白偶联受体（GNG12）悄然参与NF-κB信号的激活，这支持了癌症免疫逃逸，进而激活癌症增殖、血管生成和免疫治疗耐药性。虽然GNG12与肿瘤进展的潜在影响正在被确定，但关于GNG12在癌症免疫中的功能和机制的了解还不足。此外，GNG12与癌症相关的作用以及临床相关性长期以来一直未知；因此，对它们的识别更有可能为一种新的肿瘤抑制机制铺平道路。在本研究中，我们确定了GNG12在激活NF-κB基因中的沉默作用以及NF-κB与PD-L1表达之间的协同作用。引人注目的是，我们报告沉默GNG12基因会下调PD-L1基因的转录。因此，我们认为GNG12是多种癌症的危险因素，也是免疫治疗的一个可能靶点。
