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

Abstract

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.

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

“…Evidence provided by us and others support a critical role of the multifunctional transcription factor YY1 in oncogenesis . YY1 overexpression detected in CRC and several other solid and hematological malignancies is linked to tumor growth, proliferation, migration, and metastasis . Consistent with previous reports indicating a significant decrease in overall survival of CRC patients with high YY1 protein levels, our present findings show a clinical association among high YY1 mRNA expression, advanced tumor grade and high risk for distant metastasis; suggesting that YY1 may serve as an independent prognostic biomarker for CRC patients.…”

“…23,32 YY1 overexpression detected in CRC and several other solid and hematological malignancies is linked to tumor growth, proliferation, migration, and metastasis. [33][34][35][36][37][38][39] Consistent with previous reports indicating a significant decrease in overall survival of CRC patients with high YY1 protein levels, 25 our present findings show a clinical association among high YY1 mRNA expression, advanced tumor grade and high risk for distant metastasis; suggesting that YY1 may serve as an independent prognostic biomarker for CRC patients. On the same context, we have previously identified the critical role of YY1 as a mediator of tumor resistance to both chemo-and immunomediated apoptosis in various cancer models.…”

Prognostic significance of YY1 protein expression and mRNA levels by bioinformatics analysis in human cancers: A therapeutic target

“…The report by Potluri et al (2013) demonstrated that YY1 is overexpressed in most MM derived from patients, that YY1 is localized in the nucleus, and that there was a correlation with the repression of Bim. Their findings were confirmed by Huerta-Yepez et al (2014). The depletion of YY1 and RelA resulted in the upregulation of Bim levels and induction of apoptosis.…”

Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular carcinoma

“…Because YY1 is overexpressed in many cancers, YY1 is considered to be a potential novel prognostic marker and therapeutic target [40–42]. However, as data on its prognostic significance has become available for more human cancers, YY1′s role in tumor progression has become more controversial [32].…”