Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma

Zhang, Junqing; Yao, Qinghe; Kuang, Yongqin; Ma, Yuan; Liu, Yang; Huang, Haidong; Cheng, Jing-ming; Yang, Tao; Liu, Enyu; Liang, Liang; Fan, Kexia; Zhao, Kai; Xia, Xun; Gu, Jianwen

doi:10.1016/j.humpath.2014.01.025

Cited by 16 publications

(11 citation statements)

References 18 publications

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“…In general, whether our data are in contrast to other solid tumors (e.g. esophageal squamous-cell carcinoma, glioma), in which CREB1 expression and activation was associated with higher TNM stage and grading 46,47 , needs to be discussed. However, in Hodgkin lymphoma, CREB1 was found to be tumor suppressive by regulating key aspects of cell proliferation.…”

Section: Discussionmentioning

confidence: 85%

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

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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

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Section: Discussionmentioning

confidence: 85%

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

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“…During the last years miRs have been identified, which are deregulated by CREB or have CREB as direct target due to binding to its regulatory sequences at the 3′-UTR (Table 1). Using in silico prediction by different algorithms CREB expression could be regulated by different miRs known to be frequently downregulated in tumors, such as miR-181b, miR-128, miR-124, miR-34b, miR-23a, miR-200b, miR-203 and miR-301 [21, 46–49]. In some studies luciferase reporter assays confirmed the interaction of these miRs with the 3′-UTR of CREB.…”

Section: Molecular Basis Of Creb Regulationmentioning

confidence: 99%

“…For example miR-200b, miR-301 and miR-343 have tumor suppressive activity by targeting CREB. Overexpression of these miRs caused an inhibition of tumor cell growth and/or soft agar colony formation in vitro and a reduced tumorigenesis in vivo [49]. This could be associated with suppressed expression levels of CREB target proteins and their related pathways [47].…”

Section: Molecular Basis Of Creb Regulationmentioning

confidence: 99%

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Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target

2016

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The cyclic AMP response element binding (CREB) protein has pleiotropic activities in physiologic processes. Due to its central position downstream of many growth signaling pathways CREB has the ability to influence cell survival, growth and differentiation of normal, but also of tumor cells suggesting an oncogenic potential of CREB. Indeed, increased CREB expression and activation is associated with tumor progression, chemotherapy resistance and reduced patients' survival. We summarize here the different cellular functions of CREB in tumors of distinct histology as well as its use as potential prognostic marker. In addition, the underlying molecular mechanisms to achieve constitutive activation of CREB including structural alterations, such as gene amplification and chromosomal translocation, and deregulation, which could occur at the transcriptional, post-transcriptional and post-translational level, will be described. Since downregulation of CREB by different strategies resulted in inhibition of cell proliferation, invasion and induction of apoptosis, the role of CREB as a promising target for cancer therapy will be also discussed.

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“…Glioma is the most frequent primary malignant tumor of the adult central nervous system (CNS), and is characterized by high morbidity and poor survival [ 1 – 3 ]. Despite advances in the diagnosis and appropriate systemic therapies for glioma, including surgery, radiotherapy, and chemotherapy, there has been very little improvement in the clinical outcomes of patients with this cancer, and more than 70% of patients succumb to the disease within 2 years of diagnosis [ 4 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

HOXB1 Is a Tumor Suppressor Gene Regulated by miR-3175 in Glioma

Han

Liu

et al. 2015

PLoS ONE

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The HOXB1 gene plays a critical role as an oncogene in diverse tumors. However, the functional role of HOXB1 and the mechanism regulating HOXB1 expression in glioma are not fully understood. A preliminary bioinformatics analysis showed that HOXB1 is ectopically expressed in glioma, and that HOXB1 is a possible target of miR-3175. In this study, we investigated the function of HOXB1 and the relationship between HOXB1 and miR-3175 in glioma. We show that HOXB1 expression is significantly downregulated in glioma tissues and cell lines, and that its expression may be closely associated with the degree of malignancy. Reduced HOXB1 expression promoted the proliferation and invasion of glioma cells, and inhibited their apoptosis in vitro, and the downregulation of HOXB1 was also associated with worse survival in glioma patients. More importantly, HOXB1 was shown experimentally to be a direct target of miR-3175 in this study. The downregulated expression of miR-3175 inhibited cell proliferation and invasion, and promoted apoptosis in glioma. The oncogenicity induced by low HOXB1 expression was prevented by an miR-3175 inhibitor in glioma cells. Our results suggest that HOXB1 functions as a tumor suppressor, regulated by miR-3175 in glioma. These results clarify the pathogenesis of glioma and offer a potential target for its treatment.

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Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma

Cited by 16 publications

References 18 publications

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

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

Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target

HOXB1 Is a Tumor Suppressor Gene Regulated by miR-3175 in Glioma

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