Downregulation of CREB Promotes Cell Proliferation by Mediating G<sub>1</sub>/S Phase Transition in Hodgkin Lymphoma

Lu, Fangjin; Zheng, Ying; Donkor, Paul Owusu; Zou, Peng; Mu, Ping

doi:10.3727/096504016x14634208142987

Cited by 17 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The features of CREB in Hodgkin lymphoma (HL) strongly support its role as a tumor suppressor gene that can decelerate cell proliferation by inhibiting the expression of several cell cycle-related genes [23]. In this study, we revealed that transcription factors CREB and c-Myc positively regulated human STING gene promoter.…”

Section: Resultsmentioning

confidence: 72%

Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

et al. 2016

View full text Add to dashboard Cite

Stimulator of interferon genes (STING) plays an important role in host defense, autoimmune disease, osteoclast differentiation and anti-tumor response. Although many downstream targets have been studied in depth, the regulation of STING gene expression remains largely unknown. Here we demonstrate that transcription factors CREB and c-Myc maintain the transcriptional activity of STING. By 5′-rapid amplification of cDNA ends analysis, we identified the transcriptional start site (TSS) of STING. We illustrated that the region -124/+1 relative to TSS was sufficient for full promoter activity by a series of 5′ deletion promoter constructs. Transcriptional activity of the STING minimal promoter was dependent on CREB and c-Myc binding motifs and was abolished after mutation of these two DNA elements. Chromatin immunoprecipitation assays demonstrated that transcription factors CREB and c-Myc bind to STING promoter in vivo. Overexpression of CREB and c-Myc increased the STING promoter activity. Meanwhile, knocking-down of CREB and c-Myc by a small interfering RNA (siRNA) strategy markedly reduced endogenous STING expression. In summary, these results demonstrated that transcription factors CREB and c-Myc are involved in the regulation of STING transcription.

show abstract

Section: Resultsmentioning

confidence: 72%

Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, in Hodgkin lymphoma, CREB1 was found to be tumor suppressive by regulating key aspects of cell proliferation. The authors showed that CREB1 depletion induces the expression of cell-cycle related genes and accelerates G1/S phase transition which in turn supports oncogenesis 48 .…”

Section: Discussionmentioning

confidence: 95%

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

Friedrich

Heimer

Stoehr

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The transcription factor cAMP response element-binding protein (CREB1) has been shown to be involved in diverse biological pathways including the regulation of cell proliferation, apoptosis, cell cycle progression, and metastasis. In this context, aberrant expression of CREB1 and the functional consequences are well investigated in a number of hematopoietic and solid tumors. However, CREB1 expression and underlying control mechanisms are only poorly analyzed in renal cell carcinoma (RCC). The present study confirmed a deregulation of CREB1 protein in the clear cell type of RCC (ccRCC) and analysis of in-house ccRCC cell lines suggested a post-transcriptional control. The combination of miRNA enrichment assay, in silico analysis and molecular biological approaches revealed four novel CREB1-regulating miRNAs, namely miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p. Categorizing RCC samples as CREB1 negative or positive, respectively, the expression of these miRNAs was found to be inversely correlated with CREB1 protein levels. Analyzing 453 consecutive RCC tumors by immunohistochemistry, weakly negative, but significant correlations of CREB1 with tumor stage and grade, vascular invasion (V1) and lymphovascular invasion (L1) were found. In this respect, ccRCC might differ from other solid tumors like esophageal squamous-cell carcinoma or glioma.Renal cell carcinoma (RCC) is a kidney cancer originating in the lining of proximal renal tubular epithelial cells and can be histologically subtyped into clear cell type (ccRCC, 75%), papillary (pRCC, 13-15%), chromophobe type (chRCC, 5%), and several rare subtypes 1,2 . Globally, RCC is listed as the sixth most frequently diagnosed form of cancer in men and the tenth in women, with highest rates described in North America and the Czech Republic 3,4 . Noteworthy, RCC incidence was shown to be increasing and frequently accompanied by several risk factors including smoking, hypertension, obesity, chronic analgesic use, and diabetes 5,6 . Early treatment options for RCC are quite limited and usually involve partial or complete resection of the affected kidney(s) 7 since this type of tumor is considerably resistant to chemotherapy and radiotherapy 8 . However, immunotherapy as well as biologic or targeted therapy has shown to be an efficient option for RCC treatment 9 . Thus, it is important to characterize molecular targets responsible for the formation and development of this disease. Probably best analyzed is the alteration of the tumor suppressive Von Hippel-Lindau (VHL) gene that has a crucial value in the origin and development of ccRCC and can be found to be affected in up to 90% of all ccRCC cases 10 . Situated in a complex pathway, VHL is ultimately responsible for the regulation of the transcription factors hypoxia-inducible factor 1 alpha and 2 alpha (HIF1A, HIF2A) 11,12 . The deregulation of HIF1A and HIF2A results in the up-regulation of various growth factors like vascular endothelial growth factor (VEGF), platelet-derived growth factor beta

show abstract

“…Mutation of the Ser133 site to alanine in the endogenous CREB gene exerts a significant impact on CREB target genes in response to MSK1 activating stimuli [ 23 , 44 ]. Several studies have highlighted the important role of CREB in tumor progression and implicated its role in acute myeloid leukemia [ 45 ], acute lymphoblastic leukemia [ 46 , 47 ], myelomonocytic leukemia [ 48 ], Hodgkin lymphoma [ 49 ] and non-small cell lung cancer [ 50 , 51 ]. Here, we also found the upregulation of p-CREB in uveal melanoma tissues, indicating its role in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

MSK1 promotes cell proliferation and metastasis in uveal melanoma by phosphorylating CREB

Liu¹,

Liu²,

Wang³

et al. 2020

aoms

View full text Add to dashboard Cite

Introduction: Uveal melanoma is known as a frequent intraocular tumor, with high metastasis and poor prognosis. Mitogen-and stress-activated protein kinase 1 (MSK1) is a serine/threonine kinase that has been reported to be associated with tumor progression in several types of human cancer. However, the role of MSK1 has rarely been studied in uveal melanoma and the underlying mechanism remained unclear. Material and methods: The expression level of MSK1 in human uveal melanoma tissues and normal uveal tissues was determined by qRT-PCR analysis, western blotting and immunohistochemistry (IHC). Subsequently, MTT assay, colony formation assay and flow cytometry assay were performed to assess the effects of MSK1 on cell proliferation. Wound-healing and transwell chamber assays were adopted to clarify the role of MSK1 in cell metastasis. Finally, the function of MSK1 was confirmed in vivo in a tumor-bearing mouse model. Results: The expression levels of MSK1 and p-cyclic AMP-responsive element binding protein (CREB) were strongly up-regulated in human uveal melanoma tissues. MSK1 overexpression facilitated cell viability and clone formation, and promoted migration and invasion of uveal melanoma cells. However, mutation of cyclic AMP-responsive element binding protein (CREB) at Ser133 residues reversed the effect of MSK1 on uveal melanoma cell proliferation and metastasis. The in vivo experiment suggested that the tumor weight was lower and the tumor mass grew more slowly in the shMSK1 group as compared to the shNC group. Conclusions: MSK1 promotes proliferation and metastasis of uveal melanoma cells by phosphorylated CREB at Ser133 residues. Therefore, MSK1 could be a promising candidate for uveal melanoma therapy and especially has tremendous potential in the treatment of cancers in which the MSK1-CREB pathway is abnormally active.

show abstract

Downregulation of CREB Promotes Cell Proliferation by Mediating G₁/S Phase Transition in Hodgkin Lymphoma

Cited by 17 publications

References 29 publications

Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

MSK1 promotes cell proliferation and metastasis in uveal melanoma by phosphorylating CREB

Contact Info

Product

Resources

About

Downregulation of CREB Promotes Cell Proliferation by Mediating G1/S Phase Transition in Hodgkin Lymphoma

Cited by 17 publications

References 29 publications

Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

MSK1 promotes cell proliferation and metastasis in uveal melanoma by phosphorylating CREB

Contact Info

Product

Resources

About

Downregulation of CREB Promotes Cell Proliferation by Mediating G₁/S Phase Transition in Hodgkin Lymphoma