Frizzled Class Receptor Research Articles

Non-canonical Wnt mediated neurogenic differentiation of human bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are characterized by multipotency and self-renewal, are responsible for tissue regeneration and repair. We have previously reported in adipose tissue-derived MSCs that only Wnt5a is enhanced at neurogenic differentiation, and the mechanism of differentiation is dependent on the Wnt5a/JNK pathway; however, the role of Wnt/MAPK pathway is yet to be investigated in neurogenic differentiation in BM-MSCs. We compared the transcriptional expression of Wnt in neurogenic induced-hBM-MSCs (NI-hBM-MSCs) with that in primary hBM-MSCs, using RT-PCR, qPCR, and western blotting. Although the expression of Wnt1 and Wnt2 was unchanged, the expression of Wnt4, Wnt5a, and Wnt11 increased after neurogenic differentiation. In addition, only the expression of frizzled class receptor (Fzd) 3 gene was increased, but not of most of the Fzds and Wnt ligands in NI-hBM-MSCs. Interestingly, Wnt4, Wnt5a, and Wnt11 gene expressions significantly increased in NI-hBM-MSCs by qPCR. In addition, the protein expression level of Wnt4 and Wnt5a, but not Wnt3, increased after neurogenic induction. Furthermore, the expressions of phosphorylated-GSK-3β, ERK1/2, and PKC decreased; however, JNK was activated after neurogenic differentiation. Thus, non-canonical Wnts, i.e., Wnt4, Wnt5a, and Wnt11, regulate neurogenic differentiation through Fzd3 activation and the increase in downstream targets of JNK, which is one of the non-canonical pathways, in hBM-MSCs.

Investigating the microRNA-mRNA regulatory network in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common myelogenous malignancy in adults that is often characterized by disease relapse. The pathophysiological mechanism of AML has not yet been elucidated. The present study aimed to identify the crucial microRNAs (miRNAs/miRs) and target genes in AML, and to uncover the potential oncogenic mechanism of AML. miRNA and mRNA expression-profiling microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed and a regulatory network between miRNAs and target genes was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to predict the biological functions of the differentially expressed genes. Reverse transcription-quantitative polymerase chain reaction analysis was employed to verify the expression levels of miRNAs and target genes in AML patient samples. A total of 86 differentially expressed miRNAs and 468 differentially expressed mRNAs between AML and healthy blood samples were identified. In total, 47 miRNAs and 401 mRNAs were found to be upregulated, and 39 miRNAs and 67 mRNAs were found to be downregulated in AML. A total of 223 miRNA-target genes pairs were subjected to the construction of a regulatory network. Differentially expressed target genes were significantly enriched in the Wnt signaling pathway (hsa04310), melanogenesis (hsa04916) and pathways in cancer (hsa05200). Significantly differentially expressed miRNAs and genes, including hsa-miR-155, hsa-miR-192, annexin A2 (ANXA2), frizzled class receptor 3 (FZD3), and pleomorphic adenoma gene 1 (PLAG1), may serve essential roles in AML oncogenesis. Overall, hsa-miR-155, hsa-miR-192, ANXA2, FZD3 and PLAG1 may be associated with the development of AML via the involvement of the Wnt signaling pathway, melanogenesis and other cancer-associated signaling pathways.

Detection of Smo, Gli2 and Gli3 Among Basal Cell Carcinoma Patients in Sulaimani Province.

Basal-cell carcinoma (BCC hedgehog (Shh) of BCC. The specific downstream effector in the Shh pathway leading to cancer development is unclear. However in vertebrates, specific downstream effectors in the Shh signaling pathway including zinc-finger transcription factors Gli2 and Gli3 play the Shh pathway. S and controlled cell proliferation. The expression of transducers had not been reported yet in BCC skin of local patients. The aim of this study was to investigate the expression of S BCC biopsies taken from sun Five BCC skin biopsy specimens were taken from the sun which served as material for the study. RNA extracted from the samples, cDNA synthesised carried out and specific primers for each of the S genes were designed. Reverse transcription polymerase chain reaction (RT samples expressed genes for S patients in Sulaimani Province. These findings support the role of S the Shh–receptor complex. These results establish S oncogenes in skin and suggest a pivotal role for these transcription factors in the development of BCC. This method can be used in the diagnosis of BCC and fur study of downstream effectors in the Shh pathway may lead to an effective anti cancer therapy. Key Words: Basal cell carcinoma, Smo, Gli2, Gli3, RT-PCR. JZS (2017) 19 – 2 (Part-A) 1 Detection of Smo, Gli2 and Gli3 Among Basal Cell Carcinoma Patients in Sulaimani Province Department of Biology, College of Science, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq. Basal cell carcinoma is the most common malignancy in humans. Although rarely metasta capable of significant local destruction and disfigurement. Skin cancer is accounting for about half of all cancers occur. BCC constitute approximately 80% of all nonmelanoma skin cancers [ in the world has been reported in Australia [2]. Exposure to ult radiation is generally accepted as the major cause of BCC and the risk of this disease is significantly increased by recreational exposure to the sun during childhood and adolescence cluding fair complexion, red or blond hair, and light eye color, influence responsiveness to but are also independent risk factors [4]; exposures to ionizing radiation, arsenic, and oral methoxsalen ave also been linked to the development of BCC[5,6] Journal homepage www.jzs.univsul.edu.iq Journal of Zankoy Sulaimani Part-A- (Pure and Applied Sciences) Abstract cell carcinoma (BCC) is the most common type of cancer in human. Sonic hedgehog (Shh) signaling pathway impairment plays a key role in the pathogenesis of BCC. The specific downstream effector in the Shh pathway leading to cancer development is unclear. However in vertebrates, specific downstream effectors in e Shh signaling pathway including smoothened, frizzled class receptor (S finger transcription factors Gli2 and Gli3 play an important role in regulating the Shh pathway. SMO, Gli2, and Gli3 family proteins are necessary for adequate and controlled cell proliferation. The expression of SMO, Gli2 and Gli3 signal transducers had not been reported yet in BCC skin of local patients. The aim of this study was to investigate the expression of SMO BCC biopsies taken from sun-exposed skin areas of patients in Sulaimani Provinc Five BCC skin biopsy specimens were taken from the sun which served as material for the study. RNA extracted from the samples, cDNA synthesised carried out and specific primers for each of the S genes were designed. Reverse transcription polymerase chain reaction (RT-PCR) analyses samples expressed genes for SMO, Gli2 and Gli3 in BCC skin biopsies taken from patients in Sulaimani Province. These findings support the role of SMO, Gli2 and Gli3 as a signa receptor complex. These results establish SMO, Gli2 and Gli3 as potent oncogenes in skin and suggest a pivotal role for these transcription factors in the development of BCC. This method can be used in the diagnosis of BCC and fur study of downstream effectors in the Shh pathway may lead to an effective anti cancer therapy.

A pathway-based association study reveals variants from Wnt signalling genes contributing to asthma susceptibility.

Genetic susceptibility to asthma is currently linked to a handful of genes which have a limited ability to predict the overall disease risk, suggesting the existence of many other genes involved in disease development. Accumulated evidence from association studies in genes related by biological pathways could reveal novel asthma genes. To reveal novel asthma susceptibility genes by means of a pathway-based association study. Based on summary data from a previous a genomewide association study (GWAS) of asthma, we first identified significant biological pathways using a gene-set enrichment analysis. We then mapped all tested single nucleotide polymorphisms (SNPs) on the genes contributing to significant pathways and prioritized those with a disproportionate number of nominal significant associations for further studies. For those prioritized genes, association studies were performed for selected SNPs in independent case-control samples (n=1765) using logistic regression models, and results were meta-analysed with those from the GWAS. Two biological processes were significantly enriched: the cytokine-cytokine receptor interaction (P=0.002) and the Wnt signalling (P=0.012). From the 417 genes interacting in these two pathways, 10 showed an excess of nominal associations, including a known asthma susceptibility locus (encoding SMAD family member 3) and other novel candidate genes. From the latter, association studies of 14 selected SNPs evidenced replication in a locus near the frizzled class receptor 6 (FZD6) gene (P=9.90×10-4 ), which had a consistent direction of effects with the GWAS findings (meta-analysed odds ratio=1.49; P=5.87×10-6 ) and was in high linkage disequilibrium with expression quantitative trait loci in lung tissues. This study revealed the importance of two biological pathways in asthma pathogenesis and identified a novel susceptibility locus near Wnt signalling genes.

A bioinformatics approach for precision medicine off-label drug drug selection among triple negative breast cancer patients.

Cancer has been extensively characterized on the basis of genomics. The integration of genetic information about cancers with data on how the cancers respond to target based therapy to help to optimum cancer treatment. The increasing usage of sequencing technology in cancer research and clinical practice has enormously advanced our understanding of cancer mechanisms. The cancer precision medicine is becoming a reality. Although off-label drug usage is a common practice in treating cancer, it suffers from the lack of knowledge base for proper cancer drug selections. This eminent need has become even more apparent considering the upcoming genomics data. In this paper, a personalized medicine knowledge base is constructed by integrating various cancer drugs, drug-target database, and knowledge sources for the proper cancer drugs and their target selections. Based on the knowledge base, a bioinformatics approach for cancer drugs selection in precision medicine is developed. It integrates personal molecular profile data, including copy number variation, mutation, and gene expression. By analyzing the 85 triple negative breast cancer (TNBC) patient data in the Cancer Genome Altar, we have shown that 71.7% of the TNBC patients have FDA approved drug targets, and 51.7% of the patients have more than one drug target. Sixty-five drug targets are identified as TNBC treatment targets and 85 candidate drugs are recommended. Many existing TNBC candidate targets, such as Poly (ADP-Ribose) Polymerase 1 (PARP1), Cell division protein kinase 6 (CDK6), epidermal growth factor receptor, etc., were identified. On the other hand, we found some additional targets that are not yet fully investigated in the TNBC, such as Gamma-Glutamyl Hydrolase (GGH), Thymidylate Synthetase (TYMS), Protein Tyrosine Kinase 6 (PTK6), Topoisomerase (DNA) I, Mitochondrial (TOP1MT), Smoothened, Frizzled Class Receptor (SMO), etc. Our additional analysis of target and drug selection strategy is also fully supported by the drug screening data on TNBC cell lines in the Cancer Cell Line Encyclopedia. The proposed bioinformatics approach lays a foundation for cancer precision medicine. It supplies much needed knowledge base for the off-label cancer drug usage in clinics.

Transcriptomic study of high‑glucose effects on human skin fibroblast cells.

Skin ulcers are a common complication of diabetes mellitus (DM). Fibroblasts are located within the dermis of skin tissue and can be damaged by diabetes. However, the underlying mechanism of how DM affects fibroblasts remains elusive. To understand the effects of DM on fibroblasts, the current study mimicked DM by high‑glucose (HG) supplementation in the culture medium of human foreskin primary fibroblast cells, and the analysis of transcriptomic changes was conducted. RNA sequencing‑based transcriptome analysis identified that, upon HG stress, 463 genes were upregulated and 351 genes downregulated (>1.5‑fold changes; P<0.05). These altered genes were distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicated that 31 GO terms were enriched. Among the pathways identified, nuclear factor κB (NF‑κB) pathway genes were highly expressed, and the addition of Bay11‑7082, a typical NF‑κB signaling inhibitor, blocked the previously observed alterations in plasminogen activator inhibitor 1 (PAI1), an inflammation marker and frizzled class receptor 8 (FZD8), a Wnt signaling gene, expression that resulted from HG stress. Furthermore, an inhibitor of Wnt signaling diminished the role of Bay11‑7082 in the regulation of PAI1 expression under HG conditions, suggesting that Wnt signaling may function downstream of the NF‑κB pathway to protect fibroblast cells from HG stress. To the best of our knowledge, the current study is the first analysis of transcriptomic responses under HG stress in human fibroblasts. The data provided here may aid the understanding of the molecular mechanisms by which fibroblast cells are damaged in the skin of patients with DM.

Insights into Molecular Features of Venerupis decussata Oocytes: A Microarray-Based Study

The production of Venerupis decussata relies on wild seed collection, which has been recently compromised due to recruitment failure and severe mortalities. To address this issue and provide an alternative source of seed, artificial spawning and larval rearing programs were developed. However, hatchery-based seed production is a relatively new industry and it is still underdeveloped. A major hurdle in the European clam seed production is the control of spawning and reproduction, which is further hindered by the impossibility of obtaining fertile gametes by gonadal “stripping”, as meiosis re-initiation is constrained to a maturation process along the genital ducts. In the present study, oocytes were collected from 15 females and microarray analyses was performed to investigate gene expression profiles characterizing released and stripped ovarian oocytes. A total of 198 differentially expressed transcripts between stripped and spawned oocytes were detected. Functional analysis carried out on these transcripts highlighted the importance of a few biological processes, which are most probably implicated in the control of oocyte competence. Significant differences were observed for transcripts encoding proteins involved in meiosis progression (e.g. dual specificity phosphatase CDC25), WNT signalling (e.g. frizzled class receptor 8, wingless-type MMTV integration site family member 4), steroid synthesis (e.g. progestin and adipoQ receptor family member 3, cytochrome P450-C17), mRNA processing (e.g. zinc finger protein XlCOF28), calcium regulation (e.g. regucalcin, calmodulin) and ceramide metabolism (ceramidase B, sphingomyelinase). This study provides new information on transcriptional profiles putatively associated with ovarian egg infertility, and suggests potential mechanisms regulating early oocyte development in clams. Genes which were differentially expressed between stripped and spawned oocytes might have a pivotal role during maturation process in the gonadal duct and could be interesting targets for further functional studies aiming to make ovarian oocytes fertilizable.