KLF4 functions both as a tumor suppressor and oncogene depending on cell type. hTERT, upregulated in the majority of cancers as against its undetectable expression in differentiated cells, is one of the target genes for KLF4.
Kruppel-like factor 4 (KLF4) is a tumor suppressor gene in GC and it may interact with p53. iASPP is an evolutionarily conserved inhibitor of p53, whereas KLF4 may be negatively associated with iASPP in GC.
The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog, Bmi1, and Klf4, are known to be associated with stemness, epithelial-mesenchymal transition and aggressive tumor behavior.
By manipulating KLF4 expression in anaplastic meningioma stem-like cells, we demonstrated that KLF4 acts as a tumor suppressor during malignant progression in meningioma, affecting apoptosis, proliferation, invasion, and cell cycle.
The Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays a critical role in embryonic development, stemness and cancer, where it can act either as oncogene or tumor suppressor.
These findings provide new insights into the regulation of the miR-182 cluster expression and new opportunities for therapeutic intervention in tumors in which the KLF4-miR-182 cluster axis is deregulated.
Our studies of human HCC tissues indicated that a diminished RYBP level in the tumor (in association with altered KLF4 and Sp1 expression) was statistically associated with a larger tumor size, poorer differentiation, and an increased susceptibility to distant metastasis.
A tumorigenicity assay showed that the combination of paclitaxel treatment and KLF4 knockdown significantly decreased tumor mass originated from HTH83 cells in mice.
Taken together, our findings suggest, for what we believe is the first time, that Klf4 functions as a tumor suppressor in NPC to decrease stemness phenotype, inhibit EMT and prevent tumor progression, suggesting that restoring Klf4 function may provide therapeutic benefits in NPC.
Further studies demonstrated that when combined with decitabine the expression of acetylated histone H3 and H3K9 induced by chidamide in HL cells increased, and also the expression of tumor suppressor genes PU.1 and KLF4, which exert inhibition through apoptosis pathway.
Control and tumor specific induced pluripotent stem cells were reprogrammed with 5 reprogramming factors, Klf-4, c-Myc, Oct-4, Sox-2, and Lin-28, using the messenger RNA reprogramming system.
PhIP signature miRNAs with the profile mir-21<sup>high</sup>/mir-126<sup>low</sup>/mir-29c<sup>low</sup>/mir-215<sup>low</sup>/mir-145<sup>low</sup> were linked to reduced Klf4 levels in rat tumors, and in human pan-cancer and colorectal cancer.
The percentage of positive BIRC7 and negative KLF4 expression was significantly lower in PDAC patients with well differentiated tumors, maximum tumor size < 3 cm, no lymph node metastasis, no invasion to the surrounding tissues and organs, and TNM stage I/II stage disease than in patients with poorly differentiated tumor, maximum tumor size > 5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and TNM stage III/IV disease (P < 0.05 or P < 0.01).