scholarly journals Higher expression of Micro-RNA and Wnt signaling cascade in RNASEL candidate gene in prostate cancer

2017 ◽  
Vol 28 ◽  
pp. x176
Author(s):  
I. Hijazi ◽  
M.N. Faisal ◽  
A. Mahmood ◽  
H. Muzaffar ◽  
H. Nazir ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Wnt Signaling ◽  
Candidate Gene ◽  
Micro Rna ◽  
Signaling Cascade

scholarly journals The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4470-4477 ◽  
Author(s):  
Simona Colla ◽  
Fenghuang Zhan ◽  
Wei Xiong ◽  
Xiaosong Wu ◽  
Hongwei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Wnt Signaling ◽  
Plasma Cells ◽  
Cell Types ◽  
Signaling Cascade ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Dkk1 Expression

Abstract Multiple myeloma (MM) plasma cells, but not those from healthy donors and patients with monoclonal gammopathy of undetermined significance or other plasma cell dyscrasias involving the bone marrow, express the Wnt-signaling antagonist DKK1. We previously reported that secretion of DKK1 by MM cells likely contributes to osteolytic lesions in this disease by inhibiting Wnt signaling, which is essential for osteoblast differentiation and survival. The mechanisms responsible for activation and regulation of DKK1 expression in MM are not known. Herein, we could trace DKK1 expression changes in MM cells to perturbations in the JNK signaling cascade, which is differentially modulated through oxidative stress and interactions between MM cells with osteoclasts in vitro. Despite its role as a tumor suppressor and mediator of apoptosis in other cell types including osteoblasts, our data suggest that DKK1, a stress-responsive gene in MM, does not mediate apoptotic signaling, is not activated by TP53, and its forced overexpression could not inhibit cell growth or sensitize MM cells to apoptosis following treatment with thalidomide or lenalidomide. We conclude that specific strategies to modulate persistent activation of the JNK pathway may be beneficial in preventing disease progression and treating myeloma-associated bone disease by inhibiting DKK1 expression.

scholarly journals Association Mapping and Functional Analysis of Rice Cold Tolerance QTLs at the Bud Burst Stage

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dan Wang ◽  
Zhuo Liu ◽  
Yinghui Xiao ◽  
Xionglun Liu ◽  
Yue Chen ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Cold Tolerance ◽  
Genome Wide Association Study ◽  
Gene Knockout ◽  
Micro Rna ◽  
Negative Regulator ◽  
Bud Burst ◽  
Rab Protein ◽  
Genome Wide ◽  
Direct Seeded

AbstractCold tolerance at the bud burst stage (CTB) is a key trait for direct-seeded rice. Although quantitative trait loci (QTL) affecting CTB in rice have been mapped using traditional linkage mapping and genome-wide association study (GWAS) methods, the underlying genes remain unknown. In this study, we evaluated the CTB phenotype of 339 cultivars in the Rice Diversity Panel II (RDP II) collection. GWAS identified four QTLs associated with CTB (qCTBs), distributed on chromosomes 1–3. Among them, qCTB-1-1 overlaps with Osa-miR319b, a known cold tolerance micro RNA gene. The other three qCTBs have not been reported. In addition, we characterised the candidate gene OsRab11C1 for qCTB-1-2 that encodes a Rab protein belonging to the small GTP-binding protein family. Overexpression of OsRab11C1 significantly reduced CTB, while gene knockout elevated CTB as well as cold tolerance at the seedling stage, suggesting that OsRab11C1 negatively regulates rice cold tolerance. Molecular analysis revealed that OsRab11C1 modulates cold tolerance by suppressing the abscisic acid signalling pathway and proline biosynthesis. Using RDP II and GWAS, we identified four qCTBs that are involved in CTB and determined the function of the candidate gene OsRab11C1 in cold tolerance. Our results demonstrate that OsRab11C1 is a negative regulator of cold tolerance and knocking out of the gene by genome-editing may provide enhanced cold tolerance in rice.

scholarly journals A health disparities study of MicroRNA-146a expression in prostate cancer samples derived from African American and European American patients

2020 ◽  
Vol 10 (2) ◽  
pp. 1
Author(s):  
Monet Stevenson ◽  
Narendra Narendra Banerjee ◽  
Narendra Banerjee ◽  
Kuldeep Rawat ◽  
Lin Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Association Studies ◽  
Single Gene ◽  
Micro Rna ◽  
Genome Wide Association Studies ◽  
Racial Groups ◽  
Protein Coding ◽  
Rna Molecules ◽  
Prostate Carcinogenesis

Considering the prevalence of prostate cancer all over the world, it is desired to have tools, technologies, and biomarkers which help in early detection of the disease and discriminate different races and ethnic groups. Genetic information from the single gene analysis and genome-wide association studies have identified few biomarkers, however, the drivers of prostate cancer remain unknown in the majority of prostate cancer patients. In those cases where genetic association has been identified, the genes confer only a modest risk of this cancer, hence, making them less relevant for risk counseling and disease management. There is a need for additional biomarkers for diagnosis and prognosis of prostate cancer. MicroRNAs are a class of non-protein coding RNA molecules that are frequently dysregulated in different cancers including prostate cancer and show promise as diagnostic biomarkers and targets for therapy. Here we describe the role of micro RNA 146a (miR-146a) which may serve as a diagnostic and prognostic marker for prostate cancer, as indicated from the data presented in this report. Also, a pilot study indicated differential expression of miR-146a in prostate cancer cell lines and tissues from different racial groups. Reduced expression of miR-146a was observed in African American tumor tissues compared to those from European Whites This report provides a novel insight into understanding the prostate carcinogenesis.

Abstract 5159: Wnt signaling protein (Wisp2/CCN5) stimulates angiogenesis and invasion in prostate cancer

2011 ◽  
Author(s):  
Yasunobu Hashimoto ◽  
Rajendra K. Singh ◽  
Daniel Muñoz ◽  
Bal L. Lokeshwar
Keyword(s):  
Prostate Cancer ◽  
Wnt Signaling ◽  
Signaling Protein

scholarly journals Abi1 loss drives prostate tumorigenesis through activation of EMT and non-canonical WNT signaling

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Disharee Nath ◽  
Xiang Li ◽  
Claudia Mondragon ◽  
Dawn Post ◽  
Ming Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Wnt Signaling ◽  
Tumor Progression ◽  
Cell Line ◽  
Rna Sequencing ◽  
Cell Lines ◽  
Adaptor Protein ◽  
Prostate Tumor ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Abstract Background Prostate cancer development involves various mechanisms, which are poorly understood but pointing to epithelial mesenchymal transition (EMT) as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, acts as tumor suppressor in prostate cancer but the role of ABI1 in EMT is not clear. Methods To investigate the molecular mechanism by which loss of ABI1 contributes to tumor progression, we disrupted the ABI1 gene in the benign prostate epithelial RWPE-1 cell line and determined its phenotype. Levels of ABI1 expression in prostate organoid tumor cell lines was evaluated by Western blotting and RNA sequencing. ABI1 expression and its association with prostate tumor grade was evaluated in a TMA cohort of 505 patients and metastatic cell lines. Results Low ABI1 expression is associated with biochemical recurrence, metastasis and death (p = 0.038). Moreover, ABI1 expression was significantly decreased in Gleason pattern 5 vs. pattern 4 (p = 0.0025) and 3 (p = 0.0012), indicating an association between low ABI1 expression and highly invasive prostate tumors. Disruption of ABI1 gene in RWPE-1 cell line resulted in gain of an invasive phenotype, which was characterized by a loss of cell-cell adhesion markers and increased migratory ability of RWPE-1 spheroids. Through RNA sequencing and protein expression analysis, we discovered that ABI1 loss leads to activation of non-canonical WNT signaling and EMT pathways, which are rescued by re-expression of ABI1. Furthermore, an increase in STAT3 phosphorylation upon ABI1 inactivation and the evidence of a high-affinity interaction between the FYN SH2 domain and ABI1 pY421 support a model in which ABI1 acts as a gatekeeper of non-canonical WNT-EMT pathway activation downstream of the FZD2 receptor. Conclusions ABI1 controls prostate tumor progression and epithelial plasticity through regulation of EMT-WNT pathway. Here we discovered that ABI1 inhibits EMT through suppressing FYN-STAT3 activation downstream from non-canonical WNT signaling thus providing a novel mechanism of prostate tumor suppression.

Analysis of Predictive Value and Target Gene Prediction of Serum Micro-RNA-205 in Diagnosis and Prognosis of Prostate Cancer

2020 ◽  
Vol 12 (2) ◽  
pp. 196-201
Author(s):  
Xiangnan Hu ◽  
Xiaoliang Dou ◽  
He Wang ◽  
Jinbo Sun ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mirna Expression ◽  
Predictive Value ◽  
Expression Profiling ◽  
Target Genes ◽  
Micro Rna ◽  
Serum Samples ◽  
Serum Mirna ◽  
Diagnosis And Prognosis ◽  
Mirna Expression Profiling

The aim of this study was to explore the predictive value of serum micro-RNA (miRNA)-205 in the diagnosis and prognosis of prostate cancer, and analyze miRNA-205 target genes and functions. Eight patients diagnosed with prostate cancer or benign prostatic hyperplasia (BPH) that were treated in January 2011 were selected. The serum samples between the two groups were analyzed for miRNA expression profiling, and the differentially expressed miRNA-205 was selected for further analysis. The serum samples of 64 patients with prostate cancer and 20 patients with BPH from March 2011 to March 2013 were collected for qPCR verification. We evaluated the correlation between miRNA-205 expression level and clinicopathological data of 64 patients with prostate cancer and its prognostic value. Finally, through bioinformatic analysis, target genes of miRNA-205 were predicted, and gene ontology (GO) analysis and signal pathway analysis were performed. A total of 657 differential miRNAs were screened from miRNA expression profiling. Compared with patients with BPH, miRNA-205 showed lower expression in the serum of patients with prostate cancer. Serum miRNA-205 + PSA combined had the strongest predictive ability, 0.805. The expression level of miRNA-205 in the patients with a Gleason score ≥7 was lower than that in patients with a Gleason score <7, Low miRNA-205 expression was associated with bone metastasis and higher T stage ratings, and the 5-year overall survival rate of the low miRNA-205 expression group was lower than the high miRNA-205 expression group. A total of 27 miRNA-205 target genes were predicted. The target genes of miRNA-205 are mainly enriched in biological functions such as cell adhesion and GTP kinase activity. The target genes of miRNA-205 are mainly enriched in Axon guidance and signal transduction by L1 and other signal pathways. In this study, serum miRNA-205 was successfully identified as a potential noninvasive serum marker for diagnosis and prognosis of prostate cancer, which will be helpful for future clinical research and prostate cancer drug target design.

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