Identifying genes regulated by Kruppel-like factor-9 by RNA-seq in human glioblastoma stem cells.. Homo sapiens

Kruppel-like factor-9 (KLF9), a member of the large KLF transcription factor family, has emerged as a regulator of oncogenesis, cell differentiation and neural development; however, the molecular basis for KLF9’s diverse contextual functions remains unclear. This study focuses on the functions of KLF9 in human glioblastoma stem-like cells. We establish for the first time a genome-wide map of KLF9-regulated targets in human glioblastoma stem-like cells, and show that KLF9 functions as a transcriptional repressor and thereby regulates multiple signaling pathways involved in oncogenesis and stem cell regulation. A detailed analysis of one such pathway, integrin signaling, shows that the capacity of KLF9 to inhibit glioblastoma cell stemness and tumorigenicity requires ITGA6 repression. These findings enhance our understanding of the transcriptional networks underlying cancer cell stemness and differentiation, and identify KLF9-regulated molecular targets applicable to cancer therapeutics. Overall design: Two cell lines were used as biological replicates. Each cell line has one KLF9 induction sample and one control sample.

Kruppel样因子9（Kruppel-like factor-9）作为大型KLF转录因子家族成员，已被证实为肿瘤发生、细胞分化及神经发育的调控因子；然而，KLF9发挥多样情境依赖性功能的分子基础仍未明确。本研究聚焦KLF9在人胶质母细胞瘤干细胞样细胞中的功能。我们首次构建了人胶质母细胞瘤干细胞样细胞中KLF9调控靶点的全基因组图谱，并证实KLF9作为转录阻遏因子，可调控参与肿瘤发生及干细胞调控的多条信号通路。对其中一条通路——整合素信号通路的详细分析显示，KLF9抑制胶质母细胞瘤细胞干性与致瘤性的能力，依赖于对整合素亚基α6（ITGA6）的转录阻遏。这些发现加深了我们对癌细胞干性及分化相关转录调控网络的理解，并鉴定出可应用于癌症治疗的KLF9调控分子靶点。实验设计：本研究采用2株细胞系作为生物学重复，每株细胞系分别设置KLF9诱导组与对照组。