Kruppel-like Factor 2 Inhibits Proliferation in Renal Angiomyolipoma via IL-6/JAK/STAT3 Signaling Pathway

Anticancer Res. 2022 Oct;42(10):4753-4762. doi: 10.21873/anticanres.15980.

Abstract

Background/aim: The transcription factor Kruppel-like factor 2 (KLF2) is thought to act as a tumor suppressor. However, its expression and function in renal angiomyolipomas (AMLs) remains unclear. This study aimed to investigate the expression and function of KLF2 in AML cells.

Materials and methods: KLF2 was detected in AML tissues by immunohistochemistry and quantitative real-time polymerase chain reaction. The associations between KLF2 expression levels and clinicopathological features of patients with AMLs were analyzed. To explore its function in AMLs, KLF2 was over-expressed, and cell proliferation was assessed using cell counting kit-8 assay. Through Gene set enrichment analysis (GSEA) of RNA sequencing data, the signaling pathways regulated by KLF2 were predicted. The KLF2-regulated signaling pathway was validated by western blotting.

Results: KLF2 expression was dramatically suppressed in clinical samples of patients with AMLs. Low KLF2 expression was significantly associated with a larger tumor size and higher incidence of tumor hemorrhage (p=0.008 and p=0.009, respectively). In addition, KLF2 overexpression markedly inhibited SV7 and UMB cell survival and proliferation. GSEA and western blotting analysis revealed that KLF2 down-regulated the IL-6/JAK/STAT3 signaling pathway.

Conclusion: Collectively, KLF2 mediated AML cell growth by regulating the IL-6/JAK/STAT3 signaling pathway. These results indicate that KLF2 plays an important role in AML progression and provide novel insights into diagnostic and therapeutic biomarkers for AMLs.

Keywords: IL-6; JAK; Kruppel-like factor 2; STAT3; renal angiomyolipomas.

MeSH terms

  • Angiomyolipoma* / genetics
  • Cell Proliferation / genetics
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Kidney Neoplasms* / genetics
  • Kruppel-Like Transcription Factors* / genetics
  • Kruppel-Like Transcription Factors* / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Interleukin-6
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • STAT3 Transcription Factor
  • STAT3 protein, human