Cancer Cell International (May 2022)

KMT2B promotes the growth of renal cell carcinoma via upregulation of SNHG12 expression and promotion of CEP55 transcription

  • Jia-fu Feng,
  • Jun Wang,
  • Gang Xie,
  • Yao-dong Wang,
  • Xiao-han Li,
  • Wen-yu Yang,
  • Yu-wei Yang,
  • Bin Zhang

DOI
https://doi.org/10.1186/s12935-022-02607-w
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 13

Abstract

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Abstract Background This study aims to clarify the mechanistic action of long non-coding RNA (lncRNA) SNHG12 in the development of renal cell carcinoma (RCC), which may be associated with promoter methylation modification by KMT2B and the regulation of the 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 quantified by RT-qPCR. Subsequently, CCK-8 was used to detect cell proliferation. Wound healing assay and Transwell assay were used to detect cell migration and invasion, respectively. The in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs) was explored by matrigel-based capillary-like tube formation assay. ChIP assay was used to detect H3K4me3 in SNHG12 promoter region. The binding of E2F1 to CEP55 promoter region was analyzed with ChIP and dual luciferase reporter assays. RIP assay was used to detect the binding of SNHG12 to E2F1. Finally, the effect of SNHG12 on the tumor formation and angiogenesis of RCC was assessed in nude mouse xenograft model. Results 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 expression 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 and down-regulated the expression of CEP55, thereby inhibiting tumor formation and angiogenesis in nude mice. Conclusion The evidence provided by our study highlighted the involvement of KMT2B in up-regulation of lncRNA as well as the transcription of CEP55, resulting in the promotion of angiogenesis and growth of RCC.

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