The gene pair PRR11 and SKA2 shares a NF-Y-regulated bidirectional promoter and contributes to lung cancer development

Wang, Ying; Zhang, Ying; Zhang, Chundong; Weng, Huali; Li, Yang; Cai, Wei; Xie, Min; Long, Yinjiang; Ai, Qing; Li, Zhu; Du, Gang; Wang, Sen; Niu, Yulong; Song, Fangzhou; Ozaki, Toshinori; Bu, Youquan

doi:10.1016/j.bbagrm.2015.07.002

Cited by 50 publications

(73 citation statements)

References 39 publications

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“…Forty-eight hours after transfection, cells were lysed and their luciferase activities were measured using Dual-Luciferase assay system (Promega) as described previously51.…”

Section: Methodsmentioning

confidence: 99%

Alkaline ceramidase 2 is a novel direct target of p53 and induces autophagy and apoptosis through ROS generation

Wang

Zhang

Jin

et al. 2017

Sci Rep

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ACER2 is a critical sphingolipid metabolizing enzyme, and has been shown to be remarkably up-regulated following various stimuli such as DNA damage. However, the transcriptional regulatory mechanism of ACER2 gene and its potential role in the regulation of autophagy remain unknown. In this study, we have for the first time identified the human ACER2 gene promoter, and found that human ACER2 transcription is directly regulated by p53 and ACER2 is implicated in the induction of autophagy as well as apoptosis. A series of luciferase reporter assay demonstrated that ACER2 major promoter is located within its first intron where the consensus p53-binding sites exist. Consistently, forced expression of p53 significantly stimulated ACER2 transcription. Notably, p53-mediated autophagy and apoptosis were markedly enhanced by ACER2. Depletion of the essential autophagy gene ATG5 revealed that ACER2-induced autophagy facilitates its effect on apoptosis. Further studies clearly showed that ACER2-mediated autophagy and apoptosis are accompanied by ROS generation. In summary, our present study strongly suggests that ACER2 plays a pivotal role in p53-induced autophagy and apoptosis, and thus might serve as a novel and attractive molecular target for cancer treatment.

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“…Forty-eight hours after transfection, cells were lysed and their luciferase activities were measured using Dual-Luciferase assay system (Promega) as described previously51.…”

Section: Methodsmentioning

confidence: 99%

Alkaline ceramidase 2 is a novel direct target of p53 and induces autophagy and apoptosis through ROS generation

Wang

Zhang

Jin

et al. 2017

Sci Rep

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“…Specific short hairpin RNA-mediated depletion of PRR11 causes cell cycle arrest, leading to a significant decrease in cell viability [7]. PRR11 has been regarded as a potential new target for the diagnosis and treatment of lung cancer, as it regulates key genes associated with tumor occurrence [8,9]. However, despite growing evidence demonstrating that PRR11 is as an important cancer-related protein, the role of PRR11 in OC and the underlying molecular mechanisms have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

PRR11 Overexpression Facilitates Ovarian Carcinoma Cell Proliferation, Migration, and Invasion Through Activation of the PI3K/AKT/β-Catenin Pathway

Zhu

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ovarian cancer (OC) is the most lethal gynecologic malignancy, mainly due to the advanced stage at diagnosis in most patients and high rate of relapse. Thus, it is still essential to elucidate the underlying mechanisms and explore the diagnostic and therapeutic targets of OC. Recent studies have revealed that proline-rich protein 11 (PRR11) is dysregulated in different cancers, participating in their initiation and progression; however, it remains unclear whether PRR11 is involved in OC. Methods: Immunohistochemical staining, quantitative reverse transcription PCR, and western blotting were performed to evaluate PRR11 expression in OC tissues and cells. The relationship between PRR11 expression and the clinicopathologic data of patients were analyzed. We upregulated and downregulated PRR11 expression using a PRR11 overexpression vector and PRR11-specifc small interfering RNA, respectively, to further clarify its role in the malignant biological behavior of OC in vitro. Results: Overexpression of PRR11 in OC tissues and cells significantly correlated with advanced FIGO stage, lymph node metastasis, and large tumor size. Downregulation of PRR11 inhibited cell proliferation and prevented the invasion and migration of HO-8910 OC cells, whereas opposite results were observed in Caov3 cells upon PRR11 upregulation. Further analyses showed that PRR11 positively regulated cell proliferation-related proteins, including c-myc and cyclin D1, and increased and decreased the expression of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2, respectively. Additionally, our preliminary results demonstrated that PRR11 expression was mediated by the phosphoinositide 3-kinase/AKT/β-catenin signaling pathway. Conclusion: The results of this study provide evidence that PRR11 plays a critical role in the progression and metastasis of OC, and as such, may serve as a potential prognostic and therapeutic target in OC.

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“…In addition, a rapidly growing body of evidence has shown PRR11 as potential targets for cancer therapy [11,20]. It has been reported that MAPK signaling was involved in a variety of cancers, such as lung cancer, pancreatic cancer, prostate cancer, melanoma and colon cancer [21,22].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…PRR11 has been indicated as a potential novel target in the diagnosis and treatment of human lung cancer [11]. Through regulating important genes involved in cell cycles and tumorigenesis, PRR11 participates in the initiation and progression of lung cancer and epithelial-to-mesenchymal transition in breast cancer [11]. Our previous research showed that PRR11 widely activated in human gastric cancer, and was an independent prognostic factor for gastric cancer patients, which are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer [12].…”

Section: Introductionmentioning

confidence: 99%

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Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

Hu¹,

Song²,

Yao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gastric cancer is a highly aggressive tumor containing cancer stem cells (CSCs), which participate in tumor initiation, therapeutic resistance, and tumor relapse. Proline-rich protein 11 (PRR11) has been shown to be up-regulated in human cancers; however, its role in gastric CSCs is unknown. We hypothesize that PRR11 may affect tumorigenicity of gastric CSCs. In this study, we explored the biological function and regulation of PRR11 in gastric CSCs. Methods: Expression of PRR11 was evaluated in gastric CSC cell line by real-time quantitative PCR and western blot. The effect of PRR11 on tumorigenicity was examined by interference with gene expression using lentiviral vector-loaded shRNA. A xenograft tumor model using NOD/SCID mice was established to examine the role of PRR11 in tumor development. Results: Data showed that PRR11 was highly expressed in gastric CSCs. PRR11 was responsible for the maintenance of self-renewal and tumorigenicity of gastric CSCs, and overexpression of exogenous PRR11 could restore the self-renewal of gastric non-CSCs. Furthermore, interference with PRR11 altered the expression of stemness transcription factors. Interestingly, MAPK signaling controlled PRR11 expression by increasing PRR11 protein stability, and maintained gastric CSCs self-renewal in a PRR11 dependent manner. Conclusions: PRR11 regulated self-renewal and tumorigenicity of gastric CSCs through MAPK signaling, and could be used as a therapeutic target for gastric cancer.

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The gene pair PRR11 and SKA2 shares a NF-Y-regulated bidirectional promoter and contributes to lung cancer development

Cited by 50 publications

References 39 publications

Alkaline ceramidase 2 is a novel direct target of p53 and induces autophagy and apoptosis through ROS generation

Alkaline ceramidase 2 is a novel direct target of p53 and induces autophagy and apoptosis through ROS generation

PRR11 Overexpression Facilitates Ovarian Carcinoma Cell Proliferation, Migration, and Invasion Through Activation of the PI3K/AKT/β-Catenin Pathway

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells

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