On the other hand, tumor suppressor roles of YY1 appear to involve YY1 stimulation of tumor suppressor BRCA1, increased Bax transcription and apoptosis involving cytochrome c release and caspase-3/-7 cleavage, induction of heme oxygenase-1, inhibition of pRb phosphorylation and p21 binding to cyclin D1 and cdk4, reduced expression of long noncoding RNA of SOX2 overlapping transcript, and MUC4/ErbB2/p38/MEF2C-dependent downregulation of MMP-10.
Expression of YY1 in CSCC tissues was not significantly correlated with tumor differentiation, but was significantly correlated with an advanced clinical stage of CSCC.
Here, we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway.
Although other undiscovered mechanisms may be involved in the YY1-mediated tumor suppression role, the present study suggests that SOX2OT may act as a tumor promotor in PDAC and may represent a valuable diagnostic and therapeutic target.
Chiefly, these findings suggest that targeted inhibition of YY1 by specific small molecule inhibitors and/or the specific induction of RKIP expression and activity are potential therapeutic strategies to block tumor growth and metastasis in many cancers, as well as to overcome anticancer drug resistance.
Elevated YY1 levels were observed in patients with melanoma, compared with benign nevi and normal tissue controls, and the increased YY1 was associated with melanoma metastasis state and tumor stage.
The miR-34 family also affected tumorsphere ultra-structure and inhibited the xenografted tumor growth as well as lung metastasis of SC-M1 cells through YY1.
The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.
Analysis of patients TMA tissues with prostatic cancer revealed higher expression of both YY1 and BclXL as a function of tumor grades and their levels were directly correlated.
Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression.
Hyperactivation of YY1 in tumors was corroborated by its nuclear localization and the finding that in the tumors there were also increases in YY1AP, a YY1 coactivator not expressed in normal liver, and in survivin, as a possible target of YY1.
These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function.