Yin Yang 1 (YY1) Acting Primarily As an Oncogene and Rarely As a Tumor Suppressor in Distinct Hematological Malignancies: Prognostic and Therapeutic Implications

Yin Yang 1 (YY1) is a transcription factor that is ubiquitously expressed in many normal and cancerous tissues. This transcription factor was reported to have contradictory functions, consistent with its name, and it was shown to either activate and/or repress several gene products. The role of YY1 in cancer was initially reported to be overexpressed in a large number of solid cancers, and its overexpression was suggested to be of prognostic significance (Shi et al, Curr Cancer Drug Targets 2015;15:145-57). In addition, YY1 was also shown to be a pivotal factor in both drug and immune resistance, as well as it plays an important role in invasion and metastasis (Bonavida and Baritaki, Critical Reviews in Oncogenesis 2011;16:211-226). The reported protein expression and mRNA expressions derived from Oncomine datasets were examined to assess the functions of YY1 in a large number of hematological malignancies (Bonavida and Kaufhold, Pharmacol Ther 2015;150:149-68). However, YY1 expression was not reported in all cancer types. Our preliminary findings suggested that YY1 may act either as an oncogene or as a tumor suppressor in distinct types of hematological malignancies. In multiple myeloma (MM), YY1 protein overexpression was reported and shown to be complexed with the NF-κB subunit RelA. In addition, computational analysis revealed that increased YY1 transcript levels were observed in MM. These findings suggested that YY1 may act as an oncogene in MM, and the supporting data demonstrated that knockdown of YY1 resulted in cell death of MM cell lines. Further bioinformatic analyses showed that YY1 was overexpressed in AML patient-derived tumor tissues. In contrast to AML, bioinformatics analysis revealed that YY1 mRNA was not upregulated in chronic lymphocytic leukemia (CLL) and no significant differences were observed when compared to normal tissues. Clearly, these findings suggested that YY1 may be acting as an oncogene in AML but as a tumor suppressor in CLL. In B-cell non-Hodgkin lymphoma (NHL), the overexpression of YY1 at both mRNA and protein levels suggests its involvement in the malignant transformation. Overall, these data strongly support the notion of the oncogenic role played by the transcription factor YY1 in the majority of hematological malignancies. Accordingly, we suggest that YY1 may have important implications as a therapeutic target and as a prognostic biomarker in hematological malignancies.