The Two Sides of YY1 in Cancer: A Friend and a Foe

Abstract

Yin Yang 1 (YY1), a dual function transcription factor, is known to regulate transcriptional activation and repression of many genes associated with multiple cellular processes including cellular differentiation, DNA repair, autophagy, cell survival vs. apoptosis, and cell division. Owing to its role in processes that upon deregulation are linked to malignant transformation, YY1 has been implicated as a major driver of many cancers. While a large body of evidence supports the role of YY1 as a tumor promoter, recent reports indicated that YY1 also functions as a tumor suppressor. The mechanism by which YY1 brings out opposing outcome in tumor growth vs. suppression is not completely clear and some of the recent reports have provided significant insight into this. Likewise, the mechanism by which YY1 functions both as a transcriptional activator and repressor is not completely clear. It is likely that the proteins with which YY1 interacts might determine its function as an activator or repressor of transcription as well as its role as a tumor suppressor or promoter. Hence, a collection of YY1-protein interactions in the context of different cancers would help us gain an insight into how YY1 promotes or suppresses cancers. This review focuses on the YY1 interacting partners and its target genes in different cancer models. Finally, we discuss the possibility of therapeutically targeting the YY1 in cancers where it functions as a tumor promoter.

RETRACTED ARTICLE: HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression

“…Our gain-and loss-of-function studies indicated that HNF4A promoted aerobic glycolysis, tumorigenesis, and aggressiveness, suggesting its oncogenic roles in NB progression. Since tumor promoting or suppressive roles of transcription factors are affected by specific interacting partners [47], we believe that P1-HNF4A isoforms play different roles in tumors due to their nature of interactome, including their partners involved in gene transcription, which warrants further investigation.…”

<p>Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells</p>

“…As an ubiquitous transcription factor, Yin Yang 1 (YY1) can drive tumorigenesis, metastasis and drug resistance, and targeting YY1 is deemed to be a potential therapeutic option for various malignant tumors. 12,13 Apart from that, YY1 has been shown to be a new transcription factor regulating miRNAs. 14,15 However, it is still unknown whether miR-384 and miR-134-5p act on the role and potential mechanism of YY1 in the occurrence and invasion of GC.…”

Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets

“…Additionally, YY1 mutation or dysregulation may bring to either its downregulation or overexpression, and the alteration in YY1 intracellular levels may be linked with a wide range of conditions, including cancer [ 9 , 32 , 33 ]. The final outcome is strictly context-dependent [ 9 ].…”

“…For that reason, YY1 may exert profound effects on several important cellular pathways, including the control of cell cycle, DNA repair, chromatin recruitment of Polycomb Group (PcG) proteins, chromatin remodeling, modulation of cellular metabolism, cell survival and programmed cell death [ 6 ]. Importantly, the molecular mechanisms by which YY1 modulates the transcription of its target genes are very heterogeneous and strictly dependent on the cellular-specific context [ 7 , 8 , 9 ]. In fact, YY1 positively or negatively regulates the expression of target genes directly, by binding a conserved 12-mer consensus sequence located within the DNA transcriptional regulatory region, or indirectly, following the interaction either with other transcription factors or with co-activators/co-repressors of the transcription, as well as general epigenetic modulators [ 6 ].…”

“…It is still unclear in which cases YY1 acts as an oncogene or as a tumor suppressor. Therefore, a better comprehension of the YY1 -mediated molecular mechanisms that are activated or inhibited in the different kind of cancers may help in the development of novel diagnostics, as well as effective therapeutic strategies [ 9 ].…”