Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer

He, Junyu; Zhu, Guangchao; Gao, Lu; Chen, Pan; Long, Yuehua; Liao, Shan; Yi, Hong; Yi, Wei; Zhang, Pei; Wu, Minghua; Li, Xiaoling; Xiang, Juanjuan; Peng, Shuping; Ma, Jian; Zhou, Ming; Xiong, Wei; Zeng, Zhaoyang; Xiang, Bo; Tang, Ke; Cao, Li; Li, Guiyuan; Zhou, Yanhong

doi:10.3892/ijo.2015.3146

Cited by 46 publications

(43 citation statements)

References 40 publications

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“…The tumorigenesis of GC is a multistep process, which results from activation of oncogenes or inactivation of tumor suppressor genes [4]. Numerous studies have indicated that the development and progression of GC are due to miss-regulation of many related genes such as p53 [5], AKT [6] and PTEN [7]. Therefore, a better understanding of the molecular mechanisms involved in GC formation and development will be beneficial to discover novel therapeutic targets and develop effective strategies for the treatment of GC.…”

Section: Introductionmentioning

confidence: 99%

Rab14 Act as Oncogene and Induce Proliferation of Gastric Cancer Cells via AKT Signaling Pathway

et al. 2017

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Rab14 is a member of RAS oncogene family, and its dysfunction has been reported to be involved in various types of human cancer. However, its expression and function were still unclear in gastric cancer. The aim of this study was to investigate the function and mechanism of Rab14 in gastric cancer cell lines. Quantitative real-time PCR (qRT-PCR) was performed in 17 gastric adenocarcinoma tissues and 4 cell lines to detect the expression of Rab14. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), colony formation and flow cytometry assays were employed to determine the proliferative ability, cell cycle transition and apoptosis in vitro in BGC-823 or SGC-7901 cells. Western blot was performed to investigate the pathways and mechanism of Rab14 regulation. In this study, we show that Rab14 presents a significant up-regulated expression among the paired tissue samples and cell lines in gastric cancer. When we overexpressed Rab14 in SGC-7901 cells or silenced Rab14 in BGC-823 cells, we found that Rab14 could modify cell growth, cell cycle or apoptosis, which accompanied with an obvious regulation of CCND1, CDK2 and BAX involving in AKT signaling pathway. In conclusion, this study provides a new evidence on that Rab14 functions as a novel tumor oncogene and could be a potential therapeutic target in gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Rab14 Act as Oncogene and Induce Proliferation of Gastric Cancer Cells via AKT Signaling Pathway

et al. 2017

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“…Fra1 can be activated by inducing a variety of factors, as well as regulating several intracellular signalling pathways. 22 According to the thymus PCR chip analysis, we found that the expression of Fra1 in MG thymus was significantly increased compared to the normal thymus. From the results relating to immunohistochemistry and immunofluorescence, Fra1 positive cells were scattered in the thymic cortex and medulla, and the expression of Fra1 in mTEC, with MG thymus, was significantly higher than that of the normal thymus.…”

Section: Discussionmentioning

confidence: 92%

“…It plays an important role in accepting exogenous stimuli and regulating target gene transcription. Fra1 can be activated by inducing a variety of factors, as well as regulating several intracellular signalling pathways . According to the thymus PCR chip analysis, we found that the expression of Fra1 in MG thymus was significantly increased compared to the normal thymus.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] In our study, we screened for the higher expression of Fra1 in hyperplastic MG thymus using a gene chip, and a significant increase was detected for the expression of Fra1 in mTEC from MG thymus. Fra1 could regulate the expression of MMP-9 with STAT3 and induce the transcription of the target gene [20][21][22] ; Fra1 target genes include IL-6 and THBS. 23 These observations prompted us to analyse the role of Fra1 in TECs to investigate whether Fra1 had a regulatory effect on cytokines relating to abnormal thymocyte selection and differentiation in MG thymus.…”

Section: Introductionmentioning

confidence: 99%

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The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus

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et al. 2018

Scand J Immunol

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The thymus of a myasthenia gravis (MG) patient is often accompanied by and effected with follicular hyperplasia. Inflammatory cytokines in thymus induce the formation of germinal centres (GC). MG thymic inflammatory cytokines are predominantly secreted by stromal cells. Our previous studies revealed that the expression level of the Fra1 protein, which is a Fos member of the activator protein 1 transcription factors (AP-1), was higher in the MG thymus compared with that of the normal thymus. Based on that, we demonstrated that Fra1 was mainly expressed in medulla thymic epithelial cells (mTECs) and that the rate of Fra1 positive mTECs in the MG thymus was higher than normal. In vitro, we found that the expression of CCL-5, CCL-19 and CCL-21 could be regulated by Fra1 in mTEC and that IL-1β, IL-6, IL-8 and ICAM1 were downregulated in the Fra1 overexpression group and upregulated in the Fra1 knock-down group. Meanwhile, we detected that the expression levels of suppressor of cytokine signalling 3 (SOCS3) were significantly upregulated along with the overexpression of Fra1. Hence, we considered that the overexpression of Fra1 disrupted inflammatory cytokine secretion by mTEC in the MG thymus and that STAT3 and SOCS3 were strongly involved in this process.

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“…Fos-related antigen 1 (Fra-1) [also known as Fos-like antigen 1 ( fosl1)], a member of the Fos transcription factor family (including c-Fos, FosB, Fra-1, and Fra-2), and the JUN family (c-Jun, JunB, and JunD) can form activator protein 1 (AP-1) complexes (18,19). It has been reported that Fra-1 is the predominant protein that contributes to the activity of AP-1 (20) and plays important roles in cell proliferation, differentiation, transformation, and metastasis in cancer (21,22). More recently, others have reported that the Fra-1 transcription factor regulates several cellular processes that are implicated in inflammation and immune responses, cell proliferation and death, and extracellular remodeling (23).…”

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confidence: 99%

Fra‐1 plays a critical role in angiotensin II—induced vascular senescence

et al. 2019

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Vascular aging has a strong relationship with cardiovascular disease. Fos‐related antigen 1 (Fra‐1), also referred to as Fos‐like antigen 1, is a transcription factor and has been reported to be involved in many pathologic processes. Here, we demonstrate that Fra‐1 plays a critical role in angiotensin II (Ang II)—induced vascular senescence. Fra‐1 expression is increased significantly in Ang II—induced rat aortic endothelial cell (RAEC) senescence and the arteries from Ang II—infused mice. Interestingly, silencing Fra‐1 blocks Ang II—induced senescence phenotypes in RAECs, including decreased senescence‐associated β‐galactosidase staining, and mitigated proliferation suppression and senescence‐associated secretory phenotype. Further, knocking down Fra‐1 inhibits vascular aging phenotypes in an Ang II—infused mice model. The up‐regulated Fra‐1 also exists in human atherosclerotic plaques and Ang II—induced vascular smooth muscle cells as well as in replicated senescence RAECs. Mechanistic studies reveal that Fra‐1 preferentially associates with c‐Jun and binds to the cyclin‐dependent kinase inhibitor 1a (p21) and cyclin‐dependent kinase inhibitor 2a (p16) promoter region, leading to elevated gene expression, which causes senescence‐related phenotypes. In conclusion, our results identify that Fra‐1 plays a novel and key role in promoting vascular aging by directly binding and transcriptionally activating p21 and p16 signaling, suggesting intervention of Fra‐1 is a potential strategy for preventing aging‐associated cardiovascular disorders.—Yang, D., Xiao, C., Long, F., Wu, W., Huang, M., Qu, L., Liu, X., Zhu, Y. Fra‐1 plays a critical role in angiotensin II—induced vascular senescence. FASEB J. 33, 7603–7614 (2019). http://www.fasebj.org

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Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer

Cited by 46 publications

References 40 publications

Rab14 Act as Oncogene and Induce Proliferation of Gastric Cancer Cells via AKT Signaling Pathway

Rab14 Act as Oncogene and Induce Proliferation of Gastric Cancer Cells via AKT Signaling Pathway

The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus

Fra‐1 plays a critical role in angiotensin II—induced vascular senescence

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