Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1

Ishii, Hiroko; Hulett, Mark D.; Li, Jianmei; Santiago, Fernando S.; Parish, Christopher R.; Khachigian, Levon M.

doi:10.3892/ijo.2012.1362

Cited by 8 publications

(8 citation statements)

References 18 publications

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“…14,15 It has been reported that YY1 has an effect on the proliferation of tumor cells (such as breast carcinoma cells, glioblastoma cells) and plays an inhibitory role. 16 However, the effect of YY1 on the proliferation of pancreatic cancer remains unclear.…”

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confidence: 99%

RETRACTED: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway

Liu

Zhang

et al. 2017

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy.

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confidence: 99%

RETRACTED: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway

Liu

Zhang

et al. 2017

Intl Journal of Cancer

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“…Studies have shown YY1 positively regulated expression of several oncogenes, such as c-Myc and c-Fos[ 35 ]. In addition, YY1 can positively regulate some tumor suppressor genes, such as p21 and p16[ 36 , 37 ]. However, one study showed that YY1 was a negative cell growth regulator by inhibiting c-Myc function[ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding

Sun

Chen

2017

WJG

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AIMTo investigated the mechanism of the association between the TBX21 T-1993C promoter polymorphism and autoimmune hepatitis type 1 (AIH-1) development.METHODSIn vivo, In vivo, and reporter analyses were performed to determine the function of transcription factors binding to the T-1993C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor (T-bet) and interferon-γ (IFN-γ) expressions in CD4+ T cells, B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993TC and 15-1993TT genotype carriers, and healthy controls including 10-1993TC and 25-1993TT genotype carriers. Furthermore, a range of biochemical indices was measured simultaneously in the blood of AIH-1 patients.RESULTSTBX21-1993C allele created a strong Yin-Yang 1 (YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B cells. Higher levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the -1993 TC genotype and controls with the -1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with siRNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients.CONCLUSIONThe repression of TBX21 expression by high-affinity binding of YY1 to the -1993C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.

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“…YY1 is a zinc finger protein and a member of the GLI-Kruppel family that can activate or inactivate gene expression depending on its interacting partners (136), YY1 is overexpressed in multiple cancer types and correlates with poor clinical outcomes (137,138). However, other papers report that YY1 inhibits the cell growth in different tumor cell types in vitro, including human breast carcinoma cells and glioblastoma cells (139).…”

Section: Mitochondrial Biogenesis and Mitophagy: Mtorc1 In Cancermentioning

confidence: 99%

mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

et al. 2019

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Continuous proliferation of tumor cells requires constant adaptations of energy metabolism to rapidly fuel cell growth and division. This energetic adaptation often comprises deregulated glucose uptake and lactate production in the presence of oxygen, a process known as the "Warburg effect." For many years it was thought that the Warburg effect was a result of mitochondrial damage, however, unlike this proposal tumor cell mitochondria maintain their functionality, and is essential for integrating a variety of signals and adapting the metabolic activity of the tumor cell. The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of numerous cellular processes implicated in proliferation, metabolism, and cell growth. mTORC1 controls cellular metabolism mainly by regulating the translation and transcription of metabolic genes, such as peroxisome proliferator activated receptor γ coactivator-1 α (PGC-1α), sterol regulatory element-binding protein 1/2 (SREBP1/2), and hypoxia inducible factor-1 α (HIF-1α). Interestingly it has been shown that mTORC1 regulates mitochondrial metabolism, thus representing an important regulator in mitochondrial function. Here we present an overview on the role of mTORC1 in the regulation of mitochondrial functions in cancer, considering new evidences showing that mTORC1 regulates the translation of nucleus-encoded mitochondrial mRNAs that result in an increased ATP mitochondrial production. Moreover, we discuss the relationship between mTORC1 and glutaminolysis, as well as mitochondrial metabolites. In addition, mitochondrial fission processes regulated by mTORC1 and its impact on cancer are discussed. Finally, we also review the therapeutic efficacy of mTORC1 inhibitors in cancer treatments, considering its use in combination with other drugs, with particular focus on cellular metabolism inhibitors, that could help improve their anti neoplastic effect and eliminate cancer cells in patients. de la Cruz López et al. mTORC1 and Mitochondrial Functions Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The handling editor declared a shared affiliation, though no other collaboration, with with several of the authors AG and KC.

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Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1

Cited by 8 publications

References 18 publications

RETRACTED: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway

RETRACTED: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway

Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding

mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

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