Yin Yang 1 promotes mTORC2-mediated AKT phosphorylation

Zhang, Qiang; Wan, Meimei; Shi, Jinming; Horita, David A.; Miller, Lance D.; Kute, Timothy E.; Kridel, Steven J.; Kulik, George; Sui, Guangchao

doi:10.1093/jmcb/mjw002

Cited by 30 publications

(39 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also showed that YY1 was directly targeted by miR‐141‐3p, and ectopic expression of YY1 reversed the anti‐cancer activity of miR‐141‐3p, further supporting that YY1 functions as an oncogene in thyroid cancer. Furthermore, the downstream targets of YY1, including p53 , Snail , Myc , Fos , ERBB2 , and RKIP have been directly implicated in cancer progression (Gordon et al, ; Zhang et al, ). YY1 also regulates additional targets involved in cell proliferation and apoptosis, including EZH2, Mdm2, caspases, and HDACs (Gordon et al, ).…”

Section: Discussionmentioning

confidence: 99%

Retracted: MiR‐141‐3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via Targeting Yin Yang 1

Fang

Huang

et al. 2018

The Anatomical Record

View full text Add to dashboard Cite

has been found to be downregulated in papillary thyroid carcinoma (PTC), while little is known about the cellular functions and precise signals elicited by miR-141-3p in PTC. The results of this study indicated that the expression of miR-141-3p was aberrantly down-regulated in PTC tissues and cell lines, compared with the adjacent normal tissues and normal thyroid epithelial cells. Furthermore, the miR-141-3p expression level was negatively associated with TNM stage and lymph node metastasis in PTC. Expression of miR-141-3p effectively inhibited cell growth, promoted apoptosis, and suppressed invasion in PTC cells. Meanwhile, miR-141-3p knockdown with miR-141-3p inhibitor reversed these effects. Consistent with the in vitro study, miR-141-3p also exhibited anti-neoplastic activity in vivo. Moreover, the results revealed that miR-141-3p directly recognized the 3 0 untranslated region (3 0 UTR) of Yin Yang 1 (YY1) and negatively regulated the expression of YY1 at both protein and mRNA levels. Ectopic expression of YY1 could effectively abrogate the anti-metastatic and proapoptotic effects of miR-141-3p. In summary, the findings suggested that miR-141-3p can act as a tumor suppressor in PTC and may be a potential therapeutic target for PTC treatment. Anat Rec, 302:258-268, 2019. -3p; YY1; tumor growth; metastasis 10%-15% of patients will relapse and develop distant metastases, leading to a poor clinical outcome (Sipos and Mazzaferri, 2010). Thus, further exploring the underlying mechanisms contributing to the occurrence, progression, and metastasis of PTC may provide insight into the novel target therapies. MicroRNAs (miRNAs) belong to a group of small noncoding RNA, and play a pivotal role in various physiological and pathological processes during cancer development

show abstract

Section: Discussionmentioning

confidence: 99%

Retracted: MiR‐141‐3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via Targeting Yin Yang 1

Fang

Huang

et al. 2018

The Anatomical Record

View full text Add to dashboard Cite

show abstract

“…AKT activation can also be regulated by Yin Yang 1 (YY1) 23 . YY1, a transcription factor, can either activate 24 , 25 or repress 26 , 27 the expression of genes.…”

Section: Introductionmentioning

confidence: 99%

“…However, the expression and function of YY1 in HNSCC remain to be explored. YY1 also directly interacts with several important cancer-related regulators including AKT 23 . Moreover, overexpression of YY1 confers cancer cells with resistance in chemotherapies 36 – 39 .…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Yin Yang 1 enhances anticancer effects of cisplatin through protein phosphatase 2A-mediated T308 dephosphorylation of AKT

Zhao

Gan³

2018

Cell Death Dis

View full text Add to dashboard Cite

Cisplatin is still one of the first-line drugs for chemotherapy of head and neck squamous cell carcinoma (HNSCC) and shows a survival advantage for HNSCC. However, a substantial proportion of HNSCC eventually becomes resistance to cisplatin and the underlying mechanisms remain to be fully understood. Yin Yang 1 (YY1) is a multifunctional protein regulating both gene transcription and protein modifications and also plays a role in chemotherapy resistance. Here, we reported that knockdown of YY1 by lentivirus-mediated short hairpin RNA or tetracycline-inducible short hairpin RNA enhanced cisplatin-induced apoptosis and inhibition of cell proliferation, migration and invasion in the HNSCC cell lines, and inhibition of the xenograft tumor growth. The underlying mechanisms were revealed that knockdown of YY1 downregulated both S473 and T308 phosphorylation of AKT (protein kinase B), which was mainly responsible for cisplatin resistance, whereas overexpression of YY1 upregulated both S473 and T308 phosphorylation. Cisplatin upregulated YY1 mRNA and protein expression and both S473 and T308 phosphorylation of AKT. In the presence of cisplatin, knockdown of YY1 not only blocked cisplatin-induced increase in S473 and T308 phosphorylation of AKT, but still downregulated T308 phosphorylation. Moreover, protein phosphatase 2A (PP2A) antagonist, okadaic acid, upregulated T308, but not S473, phosphorylation, and simultaneously abolished YY1 knockdown-mediated enhancement of cisplatin-induced inhibition of cell proliferation. In addition, knockdown of YY1 promoted PP2A activity through upregulating mRNA and protein expressions of PP2A catalytic subunit alpha (PPP2CA) through the binding of YY1 in the promoter of PPP2CA. Conversely, activating PP2A by forskolin also promoted YY1 degradation and subsequently inhibited T308 phosphorylation. These results suggested that knockdown of YY1 enhanced anticancer effects of cisplatin through PP2A mediating T308 dephosphorylation of AKT, and that targeting YY1 or PP2A would enhance the efficiency of cisplatin chemotherapy in treatment of HNSCC.

show abstract

“…Overall, using cysteine mutagenesis, we discovered that ZF2 and ZF3 play an essential role in YY1-mediated transcription and cell proliferation. In addition, although multiple reports, including ours [12,13,15], revealed YY1 regulatory properties independent of its transcriptional activity, our current study unequivocally demonstrated that YY1-mediated gene expression through ZF binding to DNA is crucial and indispensable to its biological function.…”

Section: Discussionmentioning

confidence: 40%

“…YY1 can exert its function through mechanisms either dependent or independent of its transcriptional activity. We previously reported that YY1 could negatively regulate the expression of p53 and p27, and promote phosphorylation and activation of AKT [12,13,15]. Other groups reported YY1 could activate expression of many oncogenes, including MYC, ERBB2, and COX-2 [16][17][18].…”

mentioning

confidence: 99%

Functional analysis of YY1 zinc fingers through cysteine mutagenesis

Chen

Shi

et al. 2019

FEBS Letters

Self Cite

View full text Add to dashboard Cite

As a transcription factor, Yin Yang 1 (YY1) either activates or represses gene expression depending on its recruited cofactors. The YY1 C‐terminal consists of four zinc fingers (ZF) that are responsible for its DNA binding. However, the contribution of each YY1 ZF to its functions have not been fully elucidated. In this study, we used alanines to replace YY1 cysteines that are crucial to ZFs in binding to DNA. We characterized these YY1 mutants for their DNA binding, transcriptional activity, and functional role in maintaining MDA‐MB‐231 cell proliferation. We demonstrated that ZFs 2 and 3 are essential to the general biological activity of YY1. ZF 1 showed relatively low importance, while ZF 4 is virtually dispensable for YY1 function.

show abstract

Yin Yang 1 promotes mTORC2-mediated AKT phosphorylation

Cited by 30 publications

References 51 publications

Retracted: MiR‐141‐3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via Targeting Yin Yang 1

Retracted: MiR‐141‐3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via Targeting Yin Yang 1

Knockdown of Yin Yang 1 enhances anticancer effects of cisplatin through protein phosphatase 2A-mediated T308 dephosphorylation of AKT

Functional analysis of YY1 zinc fingers through cysteine mutagenesis

Contact Info

Product

Resources

About