Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma


The cover for issue 22 of Oncotarget features Figure 6, "Gene expression and correlation of KLF4 and YY1 in B-NHL," by Morales-Martinez, et al.

The clinical implications of YY1 in the transcriptional regulation of KLF4 were investigated by IHC in a TMA with 43 samples of subtypes DLBCL and FL, and all tumor tissues expressing YY1 demonstrated a correlation with KLF4 expression, which was consistent with bioinformatics analyses in several databases.

The researchers findings demonstrated that KLF4 can be transcriptionally regulated by YY1 in B-NHL, and a correlation between YY1 expression and KLF4 was found in clinical samples.

Dr. Mario I. Vega from the Molecular Signal Pathway in Cancer Laboratory at UIMEO, Oncology Hospital, Siglo XXI National Medical Center, IMSS in México City, México & the Department of Medicine, Hematology-Oncology Division at the Greater Los Angeles VA Healthcare Center, UCLA Medical Center, Jonsson Comprehensive Cancer Center, in Los Angeles, California, USA said, "Lymphoma is the sixth most common cause of cancer in terms of global incidence."

Figure 1: Bioinformatics analysis of the sequence of the promoter region of the KLF4 gene.

Recent studies have shown that KLF5 binds to consensus elements like KLF4, including one that is present in the KLF4 promoter; however, it has been reported that KLF4 is an activator element, while KLF5 represses the activity of the KLF4 promoter.

In addition, the transcription factor YY1 is expressed in lymphomas, and computational analysis has shown that its expression correlates with poor survival in lymphoma patients.

The first of The Author's approaches hypothesized that there is possible transcriptional regulation between these two transcription factors, and we presumed that YY1 can regulate the expression of KLF4.

Understanding the regulatory mechanism underlying KLF4 expression and its implications in lymphomagenesis, as well as its relationship with the transcription factor YY1, is important for diagnostic and prognostic purposes.

The biological role of KLF4 regulation by YY1 was analyzed via the use of si RNA, and KLF4 expression was determined.

The Vega Research Team concluded, "This is the first report describing a correlation between KLF4 and YY1 expression in lymphoma, and this study identifies KLF4 and YY1 as potential disease markers, which could be considered biomarkers at the time of diagnosis for predicting disease behavior. We also propose that the use of pharmacological or chemical inhibitors targeting YY1 and KLF4 could be an alternative treatment for patients with lymphoma that are known to be positive for YY1 and KLF4 expression, thus offering a therapeutic alternative for this disease."

Full text - https://doi.org/10.18632/oncotarget.26745

Correspondence to - Mario I. Vega - [email protected]

Keywords - KLF4, hematological malignancies, non-Hodgkin lymphoma, YY1, transcriptional regulation

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