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

Abstract

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. 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. 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. 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.