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

Krüppel-Like Factor 4 (KLF4) is a member of the KLF transcription factor family, and evidence suggests that KLF4 is either an oncogene or a tumor suppressor. The regulatory mechanism underlying KLF4 expression in cancer, and specifically in lymphoma, is still not understood. Bioinformatics analysis revealed two YY1 putative binding sites in the KLF4 promoter region (-950 bp and -105 bp). Here, the potential regulation of KLF4 by YY1 in NHL was analyzed. Mutation of the putative YY1 binding sites in a previously reported system containing the KLF4 promoter region and CHIP analysis confirmed that these binding sites are important for KLF4 regulation. B-NHL cell lines showed that both KLF4 and YY1 are co-expressed, and transfection with siRNA-YY1 resulted in significant inhibition of KLF4. 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. Our 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. Hence, both YY1 and KLF4 may be possible therapeutic biomarkers of NHL.

lncRNAs in Stress Response.

All living organisms sense and respond to harmful changes in their intracellular and extracellular environment through complex signaling pathways that lead to changes in gene expression and cellular function in order to maintain homeostasis. Long non-coding RNAs (lncRNAs), a large and heterogeneous group of functional RNAs, play important roles in cellular response to stressful conditions. lncRNAs constitute a significant fraction of the genes differentially expressed in response to diverse stressful stimuli and, once induced, contribute to the regulation of downstream cellular processes, including feedback regulation of key stress response proteins. While many lncRNAs seem to be induced in response to a specific stress, there is significant overlap between lncRNAs induced in response to different stressful stimuli. In addition to stress-induced RNAs, several constitutively expressed lncRNAs also exert a strong regulatory impact on the stress response. Although our understanding of the contribution of lncRNAs to the cellular stress response is still highly rudimentary, the existing data point to the presence of a complex network of lncRNAs, miRNAs, and proteins in regulation of the cellular response to stress.

Overexpression of Yin Yang 1 in bone marrow-derived human multiple myeloma and its clinical significance.

Multiple myeloma (MM) patients initially respond to conventional therapy, however, many develop resistance and have recurrences. We have reported in other tumors that the transcription factor Yin Yang 1 (YY1) is a resistant factor and, thus, we hypothesized that YY1 may be over-expressed in MM. Significantly, higher expression (staining intensity and cell frequency) of YY1 in MM cell lines and in bone marrow-derived (BM) MM from 22 MM patients was observed as compared to expression in normal BM. Higher nuclear YY1 staining was associated with disease progression. Bioinformatic analyses of mRNA in data sets corroborated the above findings and showed significant overexpression of YY1 in MM compared to normal tissues and other hematopoietic disorders. The role of YY1 expression in the regulation of drug resistance was exemplified in a drug-resistant MM cell line transfected with YY1 siRNA and which was shown to be sensitized to bortezomib-induced apoptosis. These findings highlight the potential prognostic significance of YY1 expression level in MM patients and as a therapeutic target.