scholarly journals Up-regulation of miR-24-1-5p is involved in the chemoprevention of colorectal cancer by black raspberry anthocyanins

2018 ◽  
Vol 122 (5) ◽  
pp. 518-526 ◽  
Author(s):  
He Zhang ◽  
Jun Guo ◽  
Liping Mao ◽  
Qianqian Li ◽  
Mengnan Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Black Raspberry ◽  
Differential Analysis ◽  
Human Colorectal Cancer ◽  
Colon Tissue ◽  
Downstream Target ◽  
Enhanced Expression ◽  
Regulate Protein ◽  
Regulatory Loop

AbstractAs important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.

scholarly journals Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells

2015 ◽  
Vol 112 (25) ◽  
pp. 7743-7748 ◽  
Author(s):  
Muhammad Akhtar Ali ◽  
Shady Younis ◽  
Ola Wallerman ◽  
Rajesh Gupta ◽  
Leif Andersson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Target Genes ◽  
Egf Receptor ◽  
Differentially Expressed ◽  
Striking Difference ◽  
Human Colorectal Cancer ◽  
Chip Sequencing

The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle–related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.

microRNA-146a gene polymorphism alters human colorectal cancer susceptibility and influences the expression of its target genes in toll-like receptor (TLR) pathway

Meta Gene ◽  
2020 ◽  
Vol 24 ◽  
pp. 100654
Author(s):  
Zioni Sangeetha Shankaran ◽  
Charles Emmanuel Jebaraj Walter ◽  
Arvind Ramanathan ◽  
Mohanapriya Chinambedu Dandapani ◽  
Sivakumar Selvaraj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Target Genes ◽  
Cancer Susceptibility ◽  
Toll Like Receptor ◽  
Human Colorectal Cancer

scholarly journals Disruption of LTBP-4 function reduces TGF-β activation and enhances BMP-4 signaling in the lung

2004 ◽  
Vol 167 (1) ◽  
pp. 123-133 ◽  
Author(s):  
Katri Koli ◽  
Frank Wempe ◽  
Anja Sterner-Kock ◽  
Anna Kantola ◽  
Martina Komor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Matrix ◽  
Lung Development ◽  
Target Genes ◽  
Bone Morphogenic Protein ◽  
Lung Fibroblasts ◽  
Mouse Lung ◽  
Wild Type ◽  
Enhanced Expression ◽  
Tgf Β1

Disruption of latent TGF-β binding protein (LTBP)–4 expression in the mouse leads to abnormal lung development and colorectal cancer. Lung fibroblasts from these mice produced decreased amounts of active TGF-β, whereas secretion of latent TGF-β was significantly increased. Expression and secretion of TGF-β2 and -β3 increased considerably. These results suggested that TGF-β activation but not secretion would be severely impaired in LTBP-4 −/− fibroblasts. Microarrays revealed increased expression of bone morphogenic protein (BMP)–4 and decreased expression of its inhibitor gremlin. This finding was accompanied by enhanced expression of BMP-4 target genes, inhibitors of differentiation 1 and 2, and increased deposition of fibronectin-rich extracellular matrix. Accordingly, increased expression of BMP-4 and decreased expression of gremlin were observed in mouse lung. Transfection of LTBP-4 rescued the −/− fibroblast phenotype, while LTBP-1 was inefficient. Treatment with active TGF-β1 rescued BMP-4 and gremlin expression to wild-type levels. Our results indicate that the lack of LTBP-4–mediated targeting and activation of TGF-β1 leads to enhanced BMP-4 signaling in mouse lung.

scholarly journals Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer

2019 ◽  
Vol 20 (22) ◽  
pp. 5758 ◽  
Author(s):  
Liye Wang ◽  
Kwang Bog Cho ◽  
Yan Li ◽  
Gabriel Tao ◽  
Zuoxu Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Rna Transcripts ◽  
Competitive Endogenous Rnas

Colorectal cancer (CRC) is the third most common cancer and has a high metastasis and reoccurrence rate. Long noncoding RNAs (lncRNAs) play an important role in CRC growth and metastasis. Recent studies revealed that lncRNAs participate in CRC progression by coordinating with microRNAs (miRNAs) and protein-coding mRNAs. LncRNAs function as competitive endogenous RNAs (ceRNAs) by competitively occupying the shared binding sequences of miRNAs, thus sequestering the miRNAs and changing the expression of their downstream target genes. Such ceRNA networks formed by lncRNA/miRNA/mRNA interactions have been found in a broad spectrum of biological processes in CRC, including liver metastasis, epithelial to mesenchymal transition (EMT), inflammation formation, and chemo-/radioresistance. In this review, we summarize typical paradigms of lncRNA-associated ceRNA networks, which are involved in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the competitive crosstalk among RNA transcripts and the novel targets for CRC prognosis and therapy.

scholarly journals Influence of JAK2V617F allele burden on clinical phenotype of polycythemia vera patients: A study from India

2019 ◽  
Vol 08 (02) ◽  
pp. 127-129
Author(s):  
Sudha Sazawal ◽  
Kanwaljeet Singh ◽  
Sunita Chhikara ◽  
Rekha Chaubey ◽  
Manoranjan Mahapatra ◽  
...  
Keyword(s):  
Target Genes ◽  
Clinical Phenotype ◽  
Myeloproliferative Neoplasms ◽  
Treatment Protocol ◽  
Allele Burden ◽  
Downstream Target ◽  
Chronic Myeloproliferative Neoplasms ◽  
Enhanced Expression ◽  
The Impact ◽  
Jak2v617f Allele Burden

Abstract Background: Elevated JAK2V617F allele burden is associated with enhanced expression of downstream target genes in Philadelphia negative chronic myeloproliferative neoplasms (CMPNs) which include PV, ET & PMF. Previous studies have shown the impact of JAK2V617F allele burden on clinical phenotype of CMPNs. However, there is no data from India regarding the association between JAK2V617F allele burden and clinical phenotype in PV. Aims/Settings and Design: We aimed to investigate the effect of allele burden on clinical phenotype in 90 JAK2V617F positive PV patients and to see its influence on disease related complications. Material and Methods: Allele burden of 90 JAK2V617F positive PV patients was quantified by Real-time polymerase chain reaction (RQ-PCR). Results: 74/90 (82.22%) were males and 16/90 (17.78%) were females (median 45 years, range 35-78). Patients with age >50 years had significantly higher JAK2V617F allele burden (median 40.15%, range 0.49–91.62 %) than patients with ≤ 50 years age (median 48.59 %, range 0.56–86.74 %; P < 0.032). Patients with splenomegaly had significantly higher JAK2V617F allele burden (mean 50.24%, range 6.91–84.17%) than patients without splenomegaly (mean 33.82 %, range 0.49–71.83 %; P < 0.017). Patients with higher allele burden (median 57.20, range 43.4–72.03%) had significantly raised thrombotic events than the patients with lower allele burden (median 37.38, range 0.49–84.17% P < 0.043). 49/90 (54%) were homozygous and 41/90 (46%) were heterozygous. Conclusions: Higher JAK2V617F allele burden showed association with increased age, splenomegaly and thrombotic events. Thus, it may be considered for prognostication and setting up the treatment protocol in PV patients.

scholarly journals Diverse LEF/TCF Expression in Human Colorectal Cancer Correlates with Altered Wnt-Regulated Transcriptome in a Meta-Analysis of Patient Biopsies

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 538 ◽  
Author(s):  
Claus-Dieter Mayer ◽  
Soizick Magon de La Giclais ◽  
Fozan Alsehly ◽  
Stefan Hoppler
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Target Genes ◽  
Meta Analysis ◽  
Cellular Transformation ◽  
Colorectal Tumor ◽  
Human Colorectal Cancer ◽  
Tumor Sample

Aberrantly activated Wnt signaling causes cellular transformation that can lead to human colorectal cancer. Wnt signaling is mediated by Lymphoid Enhancer Factor/T-Cell Factor (LEF/TCF) DNA-binding factors. Here we investigate whether altered LEF/TCF expression is conserved in human colorectal tumor sample and may potentially be correlated with indicators of cancer progression. We carried out a meta-analysis of carefully selected publicly available gene expression data sets with paired tumor biopsy and adjacent matched normal tissues from colorectal cancer patients. Our meta-analysis confirms that among the four human LEF/TCF genes, LEF1 and TCF7 are preferentially expressed in tumor biopsies, while TCF7L2 and TCF7L1 in normal control tissue. We also confirm positive correlation of LEF1 and TCF7 expression with hallmarks of active Wnt signaling (i.e., AXIN2 and LGR5). We are able to correlate differential LEF/TCF gene expression with distinct transcriptomes associated with cell adhesion, extracellular matrix organization, and Wnt receptor feedback regulation. We demonstrate here in human colorectal tumor sample correlation of altered LEF/TCF gene expression with quantitatively and qualitatively different transcriptomes, suggesting LEF/TCF-specific transcriptional regulation of Wnt target genes relevant for cancer progression and survival. This bioinformatics analysis provides a foundation for future more detailed, functional, and molecular analyses aimed at dissecting such functional differences.

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