SNHG12 Regulated by KMT2B Participates in the Pathogenesis of Renal Cell Carcinoma via E2F1/CEP55

Abstract

Objective: This study is to investigate the regulation of long non-coding RNA (lncRNA) SNHG12 promoter methylation modification by KMT2B and the mechanism of SNHG12 in the development of renal cell carcinoma (RCC) involving E2F1/CEP55 axis.Methods: TCGA and GEO databases were used to predict the involvement of SNHG12 in RCC. Knockdown of SNHG12/E2F1/CEP55 was performed. Next, SNHG12 expression and other mRNAs were analyzed by RT-qPCR. Subsequently, CCK-8 was used to detect cell proliferation. Wound healing test and Transwell assay was used to detect cell migration and invasion, respectively. The vascularization of HUVEC was explored by in vitro pseudotubule formation. CHIP was used to detect H3K4me3 in SNHG12 promoter region. The binding of E2F1 and CEP55 promoter region was analyzed with CHIP and dual luciferase reporter assay. RIP was used to detect the binding of SNHG12 and E2F1. Finally, the effect of SNHG12 on the tumor formation and angiogenesis of RCC was assessed in nude mouse xenograft model.Results: Bioinformatics analysis showed that SNHG12 was highly expressed in RCC tissues and cells, and it was related to the poor prognosis of RCC patients. SNHG12 knockdown significantly inhibited RCC cell proliferation, migration, and invasion and HUVEC angiogenesis. KMT2B up-regulated SNHG12 through modifying H3K4me3 in its promoter region. In addition, SNHG12 promoted CEP55 expression by recruiting the transcription factor E2F1. Knockdown of SNHG12 blocked E2F1 recruitment, thereby down-regulating the expression of CEP55, and inhibited tumor formation and angiogenesis of RCC cells in nude mice.Conclusion: KMT2B up-regulates SNHG12 via the modification of H3K4me3 in its promoter region. SNHG12 recruits E2F1 to promote the expression of CEP55, and ultimately promotes RCC cell proliferation, migration, and invasion and HUVEC angiogenesis.