Yin Yang-1 increases apoptosis through Bax activation in pancreatic cancer cells

Zhang, Jingjing; Zhu, Yaping; Yang, Chuang; Liu, Xian; Peng, Yunpeng; Jiang, Kuirong; Miao, Yi; Xu, Zekuan

doi:10.18632/oncotarget.8654

Cited by 31 publications

(39 citation statements)

References 27 publications

(25 reference statements)

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“…[33][34][35] According to our previous study, YY1 is highly expressed and plays the role of a tumor suppressor factor in pancreatic cancer. 14,15 It has been found that high expression of YY1 can inhibit the invasion and metastasis and promote the apoptosis in pancreatic cancer cells. 14,15 In this study, we reveal that YY1 suppresses the abilities of proliferation and migration in pancreatic cancer cells, which is consistent with the anticancer role of YY1in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Human pancreatic ductal adenocarcinoma (PDAC) cell lines BXPC‐3 and PANC‐1 were acquired from the Shanghai Cell Bank (Shanghai, China). Previously, the stable cells of YY1 overexpression or knockdown were already constructed in BXPC‐3 and PANC‐1 cell lines, and the stable cell lines (BXPC‐3‐Vector, BXPC‐3‐YY1, BXPC‐3‐Scramble shRNA, BXPC‐3‐YY1 shRNA, PANC‐1‐Vector, PANC‐1‐YY1, PANC‐1‐Scramble shRNA and PANC‐1‐YY1 shRNA) were selected by culturing in media containing 5 μg/ml puromycin (Sigma, St Louis, MO) . YY1 expression was confirmed by qRT‐PCR and Western blot.…”

Section: Methodsmentioning

confidence: 99%

“…The reporter gene plasmid has been constructed as described above, and transfections were performed using Lipofectamine 3000 according to the manufacturer's protocol. For luciferase activity assay, the experiment was performed as described previously . Renilla luciferase reporter vector pRL‐SV40 was used as an internal control (Promega, Madison, WI) and its luciferase activity were normalized to firefly luciferase activity.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…MDM2 is an oncoprotein, which blocks p53‐mediated transactivation (Mendoza, Mandani, & Momand, ) and has been revealed to be amplified in PC (Dong et al, ). Bax is known as a multidomain proapoptotic protein, and its higher expression signifies better outcomes for PC patients (Haneef, Parvathy, Thankayyan, Sithul, & Sreeharshan, ; J. J. Zhang et al, ). p21 is a crucial target gene of p53 in executing cell cycle arrest (Y. Zhang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer

Zhang

et al. 2018

Journal Cellular Physiology

159

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Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase-9, caspase-3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β-Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase-9, caspase-3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase-9, caspase-3, p53, and p21. The shCCNB1 group had decreased proliferation and S-phase cell proportion and increased apoptosis, senescence, and G0/G1-phase cell proportion. The PFT-α group showed higher expressions of MDM2 and lower expressions of Bax, caspase-9, caspase-3, p53, and p21. The PFT-α group had increased proliferation and S-phase cell proportion and declined apoptosis, senescence, and G0/G1-phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.

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“…As a key transcription factor, YY1 regulates its target gene transcription in a very complex manner. YY1 can activate transcription of oncogenes and tumor suppressors, such as c‐Myc , c‐Fos , ERBB2 , cyclooxygenase‐2 , OTX2 , Msx2 , and Bax . YY1 can also repress transcription of oncogenes and tumor suppressors including Has2 , HIF‐2 α , PVT1 , CEBPD , p16(INK4a) , and RB etc.…”

Section: Discussionmentioning

confidence: 99%

YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress

Sun

et al. 2017

Cancer Medicine

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Human MYCT1 cDNA was first cloned using in silicon hybridization and molecular methods and previously AbstractYY1 is a key transcription factor and plays different roles in various cancers. However, role and mechanism of YY1 in laryngeal cancer are still unknown. YY1 and MYCT1 mRNA and protein levels were detected by Real-time RT-PCR and Western Blot methods, respectively. Binding of YY1 to MYCT1 promoter was predicted and confirmed by bioinformatics and chromatin immunoprecipitation assays, respectively. MYCT1 promoter activity was assessed by dual luciferase assay system. Laryngeal cancer cell proliferation, migration, and apoptosis were evaluated by cell viability, colony formation, cell scratch assay, transwell assay, and flow cytometry methods, respectively. YY1 and MYCT1 were upregulated and downregulated at transcriptional level in laryngeal cancer, respectively, which showed a negative correlation between YY1 and MYCT1 expression in laryngeal cancer. Significantly higher expression of YY1 and lower expression of MYCT1 were found in laryngeal cancer tissues of patients with lymphatic metastasis than those without metastasis.YY1 directly bound to MYCT1 promoter region and inhibited its promoter activity. YY1 silence had similar biological functions as MYCT1 overexpression in repressiveness of proliferation and migration, and promotion of apoptosis in laryngeal cancer cells. However, the effects of YY1 silence were recovered by MYCT1 knockdown. YY1 promotes proliferation and migration with suppression of apoptosis via directly inhibiting MYCT1 in laryngeal cancer cells, suggesting that YY1 is a useful target as a potential oncogene in laryngeal cancer development and progression. implying that MYCT1 function in cancer is tissue-specific. For example, MYCT1 is downregulated and promotes apoptosis in laryngeal and gastric cancer [1,2]. However, MYCT1 is upregulated and enhances cancer cell viability in acute myeloid leukemia [3]. Therefore, study on MYCT1 regulation network helps us to understand the tissuespecific manner of MYCT1 in cancer.At present, several transcription factors have been reported to be a direct regulator of MYCT1. In our and other studies, C-MYC directly targets MYCT1 promoter region and regulates its expression [1,[4][5][6]. We also found that MYCT1 promoter region including C-MYC binding site is hypermethylated in laryngeal cancer, suggesting that the methylation status interferes with the binding of C-MYC to MYCT1 leading to MYCT1 dysregulation in laryngeal cancer [7]. Liddiard et al. discovered that the fusion protein RUNX-ETO contributes to key aspects of the leukemic phenotypes via targeting MYCT1 [3]. In addition to C-MYC and RUNX-ETO, other transcription factors regulating MYCT1 expression are not reported.YY1 (Yin-Yang-1) is a zinc-finger transcription factor that belongs to the GLI-Krüppel gene family [8] and abnormally expressed in lots of cancer such as colon cancer [9], non-small-cell lung cancer [10], and myeloma [11], indicating that it has key roles in carcinogenesis. Ho...

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Yin Yang-1 increases apoptosis through Bax activation in pancreatic cancer cells

Cited by 31 publications

References 27 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

Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer

YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress

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