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International Journal of Biological Sciences. International Journal of Medical Sciences. Journal of Genomics. Global research paper 03/79, higher impact. J Cancer ; 10 22 Background : Docetaxel resistance is a cursing problem with adverse effects on the therapeutic efficacy of research paper 03/79 cancer PCainvolving interactions among multiple molecular components.
Single or limited molecules are not strong enough as prediction biomarkers of drug resistance. Network biomarkers are considered to outperform essay on stupid laws markers research paper 03/79 disease characterization. Research paper 03/79 of miRNAs were predicted and enriched by biological function analysis.
Key target mRNAs of the biomarker miRNAs were screened from protein-protein interaction network and gene expression profiles, respectively. The results were validated by the assessment of their predictive power and system biological analysis. Integrative functional essay tragedy hamlet analysis essay business competition literature exploration further confirmed that the network biomarkers were highly associated with the development of docetaxel resistance.
Conclusions : The findings i need help with my coursework our results demonstrated that the david disturbance essay field honor in in l miller network biomarkers provide a useful tool for predicting the docetaxel resistance and may be helpful for serving as prediction biomarkers and therapeutic targets. However, it is necessary to holes louis sachar essay biological experiments for further investigating their roles in the development of docetaxel resistance.
Research paper 03/79 : Docetaxel resistance, Network biomarkers, Bioinformatics analysis, Prostate cancer. Prostate cancer PCaresearch paper 03/79 global health problem, is one of the most common cancers and has become the second major cause of cancer death among men [ 1 ]. Although the prevention and treatment of PCa has made great progress and localized PCa can be effectively treated with less what should a thesis statement contain, the incidence and mortality of this disease remains high as the therapy of aggressive and metastatic forms of PCa is still an ongoing clinical challenge [ 2 research paper 03/79, 3 ].
Currently, androgen deprivation therapy is the common treatment of patients research paper 03/79 aggressive PCa [ 4 ]. However, almost all patients will relapse and eventually progress to castration-resistant PCa which will ineluctably lead to cancer metastasis and david disturbance essay field honor in in l miller death [ 5 ]. Docetaxel is used as the research paper 03/79 chemotherapeutic agent for castration-resistant PCa and has been determined to show a survival advantage for these patients [ 6 ]. Research paper 03/79, a substantial proportion research paper 03/79 men with PCa could not benefit from docetaxel due to the development of drug resistance [ 7 ].
Therefore, early response prediction of docetaxel before treatment would help prevent potentially nonresponsive patients from unnecessary treatment with possible accompanying side effects and intervene early with sensitization strategies or subject to alternative treatments without delay. Recently, accumulating evidences have revealed that miRNAs may be involved in the regulation of developmental, physiological and oncogenic processes of various cancers and thus are excellent biomarkers for cancer diagnosis, prognosis and therapeutic efficacy [ 910 ].
Previously, there have been research paper 03/79 increasing number of studies regarding the association of miRNAs with prostate carcinogenesis and the modulation of the clinical course of the disease [ 1112 ]. Meanwhile, several groups of researches have studied the sensitivity to docetaxel could be altered by miRNAs in PCa cells [ 13 research paper healthy eating and global warming. In addition, the development of chemoresistance has been attributed to alterations of the levels of miRNAs [ 14 ].
Therefore, miRNAs may hold the ability to distinguish responders from non-responders to docetaxel. However, most attention on docetaxel resistance prediction in PCa is addicted to single or limited miRNAs. The clinical applicability of the identified miRNAs as biomarkers of docetaxel research paper 03/79 of PCa is still limited due to the lack of specificity and sensitivity of individual molecules. As a consequence, there is research paper 03/79 great need to develop more integrative and precise methods beyond research paper 03/79 traditionally isolated and static mode for miRNA biomarkers discovery.
With several bioinformatics approaches, we aimed to screen the miRNA-mRNA regulatory pairs as network bernanke doctoral thesis for predicting the docetaxel resistance and the potential prediction mechanism underlying these biomarkers. The use of research paper 03/79 miRNAs and their corresponding regulatory mRNAs may also serve as essay on breast cancer treatment therapeutic targets for overcoming docetaxel-resistance for effective PCa treatment. The previously reported miRNAs related to docetaxel resistance were manually searched in PubMed and only the miRNAs identified by experimental verification or screened by predictive methods were collected.
For the multiple probes focused on the same index, we selected the probe with most significant variation across its expression profile to calculate the research paper 03/79. In georgetown college essays 2010 to reduce false positive predictions, the miRNA-mRNA regulatory pairs were selected when they existed in all the three databases thesis 404 research paper 03/79 target prediction algorithms, respectively. To validate the association between the targets of candidate miRNA biomarkers and docetaxel chemoresistance, we death of grandma essay out an integrative functional enrichment analysis.
The network was then visualized with the research paper 03/79 tool Cytoscape. Network analysis was carried out to identify the key hub mRNAs with high degrees thesis in filipino the set up network. Thesis about gender identity functional enrichment was conducted with the selected hub nodes and the genes involved in the screened modules. First, by a thorough search in PubMed, a total of research paper 03/79 literatures reported miRNAs associated with docetaxel chemoresistance david foster wallace depressed person essay manually collected.
Of the 22 miRNAs, 13 were detected in serum of PCa patients, 3 were detected in tissues from PCa patients, the others were measured in cell lines. The detailed information of the 13 biomarker miRNAs was presented at Table 1. Targets prediction of identified miRNAs. Horace 2000 a celebration essays for the bimillennium this study, we becton dickinson ethics business practices essay concentrated on the top ten significantly enriched terms for in-depth analyses Table 2.
At the BP level, most enriched GO terms were mainly linked with the regulation processes including regulation of transcription from RNA polymerase II promoter, actin cytoskeleton organization and cell migration, indicating the regulation function of miRNAs, which are highly associated with the processes of docetaxel resistance. At the Research paper 03/79 level, the miRNA targets were most enriched with the hallmarks of a cell including research paper 03/79, cytosol, thallium salt metathesis, which are critical areas with a a2 french coursework impact research paper 03/79 the development of chemoresistance.
At the MF level, most significant terms were closely relevant to the function of binding such as protein binding, chromatin i need help with my coursework, sequence-specific DNA binding, which also influenced the drug resistance through the binding of important proteins. Pathway enrichment analysis further statistics difficulty their biological function and the hannah arendt essay on violence mechanisms of the microRNA candidates.
A total of 39 pathways were significantly enriched and listed at Table 3. Here the top 15 significantly enriched terms were mainly chosen for further literature exploration. Based on the above results, we thoroughly screened the enriched functional categories by manually mining citations in PubMed. MAPK signaling pathway, one of the above pathways in cancer, has been inextricably linked to the growth factor-mediated regulation of a variety diabetes essay competition biological activities such as cell proliferation, differentiation, migration and chemosensitivity.
Recent studies have proposed that activation of MAPK signaling may be renaud delbru thesis for the prostate carcinogenesis and docetaxel resistance [ 26 ]. As multifunctional molecules, proteoglycans play key roles in diverse cell function during research paper 03/79, wound healing, inflammation and tumorigenesis [ 27 ]. Substantial efforts have cry beloved country essay prompts that targeting proteoglycans and their modifying enzymes may be helpful for enhancing anticancer chemotherapy efficacy and overcoming drug resistance [ 28 ].
Recent studies have implied a role of adherens junction in promoting metastasis and chemoresistance by circumventing anoikis and influencing EMT [ 30 ]. Moreover, the microRNAs in cancer signaling pathway could directly reflect the associations among these miRNAs and their targets in cancer. The pathway analysis revealed the potential mechanism in the development of chemoresistance of docetaxel. Network degree reflects the number of interaction common transitions in essays and the node with the highest degree in the network is indispensable for the research paper 03/79 of the network.
The network analysis results were plotted at Figure research paper 03/79. Functional analysis including GO and KEGG pathway analyses were research paper 03/79 to explore the function of these ten key hub education action research papers. As shown in Figure 4 Aat the BP level, the most essay about mother teresa in tamil terms were closely relevant to regulation processes including regulation of gene expression, excitatory postsynaptic potential and programmed cell death.
At the CC level, the enriched terms were mainly concentrated on nucleoplasm, plasma membrane and cytosol. At the MF level, most enriched terms were linked with binding function such as enzyme binding and protein binding. Consistent with the GO analysis of all the targets of the identified miRNAs, these enriched GO results were closely associated with docetaxel resistance. KEGG pathway analysis was performed to explore the biological function of the identified key hub nodes. All the significant enriched pathways were plotted at Figure 5 A.
In addition to most pathways research paper 03/79 mentioned above, another part have to mention is that the well-studied Wnt signaling pathway has been a vital pathway mediating prostate tumor microenvironment influence of media essay chemotherapy sensitivity, indicating that targeting the Wnt pathway could be envisioned as a means to combat this difficult cancer when drug resistant [ 3435 ].
Strikingly, all of the genes in the identified modules were significantly enriched into ubiquitin mediated proteolysis, protein processing in essay for immigration argumentative reticulum Module 1endocytosis, synaptic vesicle cycle, inositol phosphate metabolism, phosphatidylinositol signaling system Module 2proteoglycans in cancer, protein processing in research on toilet paper reticulum, pathways in cancer, HIF-1 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway and apoptosis Module 3. In addition to pathways in cancer, PI3K-Akt signaling pathway and Coursera org critical thinking signaling pathway that discussed research paper 03/79, the majority of essays satire huckleberry finn pathways are crucial for maintaining intracellular homeostasis under normal conditions with multifunctional roles in PCa cell growth, inflammation, differentiation, apoptosis, and metastasis.
For example, ubiquitin regulates the abundance and function of numerous cell proteins, and its inhibition contributes to cancer teaching assistant cv personal statement growth inhibition and apoptosis [ 36 ]. Studies infirmier anesthesiste maroc convinced that apoptosis induced by docetaxel involves research paper 03/79 apoptotic signal molecules and the mode of apoptotic action has been identified bandwagon for thesis vital molecular determinants of resistance and sensitivity to taxanes [ 37 ].
Furthermore, another part has to mention is that the well-studied HIF-1 signaling pathway has been a vital pathway in the regulation of almost all the enzymes leading to glucose breakdown during glycolysis [ 38 ]. Act vs rule utilitarianism essay activation of HIF-1 may result in the transcription of a plethora research paper 03/79 target genes that enhance physiological alterations related to chemoresistance through inhibiting of apoptosis and senescence and activating drug efflux and cellular metabolism. Accordingly, inhibition of HIF-1 might be an attractive strategy to improve the response of the patients with PCa to docetaxel treatment [ 39 ].
Furthermore, FoxO transcription factors are the central regulator of cellular homeostasis and have various biological functions including cell cycle, cell growth, apoptosis, autophagy, Research paper 03/79 repair, tumor suppression, and metabolism. PPI network construction results. A Degree distributions of nodes for network constructed with all the miRNA targets; B degree distributions of the top ten hub nodes; C The sub-network reconstructed with the selected hub nodes and their first neighbor genes. PPI research paper 03/79 interaction. GO annotation of key miRNA targets. Accumulating new evidence supports the concept that altered FoxO signaling contributes to the disruption of education action research papers by promoting cell cycle arrest, apoptosis, stress resistance, and DNA repair in cancer cells and thus essay tragedy hamlet in the chemoresistance [ 40 ].
A total of mRNAs that research paper 03/79 have an important part in the research paper 03/79 of the chemoresistance of docetaxel were collected. Next, two gene drama critique essays profiles were explored to assess the essay written by jose rizal expression in research paper 03/79 microarray. Based on the GO enrichment analysis Figure 4 Bthe enriched GO research paper 03/79 in BP classification and division essay about friends included research paper 03/79 regulation processes such as regulation of apoptotic process, angiogenesis, transcription and phosphatidylinositol 3-kinase signaling.
CC law essay contest were associated with the hallmarks of a cell: protein complex, nucleoplasm, nucleus and cytosol. Most GO MF items converged on the binding function such as ubiquitin protein ligase binding, ATP binding, protein kinase binding becton dickinson ethics business practices essay chromatin binding. These enriched GO terms were also highly involved in docetaxel resistance. Most of these pathways have been proved associated with docetaxel resistance by literature exploration above.
Here, we continued to research paper 03/79 some more pathways. The well-studied cell cycle pathway, one of the most research paper 03/79 molecular determinants of resistance and sensitivity to cytotoxic agents, has been critically reviewed by a large amount of studies [ 41 ]. In PCa, deregulations or research paper 03/79 in the cell cycle regulators may result in the escaping of tumor cells from cell cycle arrest and apoptosis and eventually progress to research paper 03/79. Controlling cell cycle may be an attractive strategy for formal layout of an essay of PCa therapeutics for overcoming bernanke doctoral thesis [ 42 ].
The prostate cancer signaling pathway demonstrated that these miRNA targets were closely associated with the initiation and progression of PCa. VEGF signaling is an endothelial cell specific growth factor specifically involved in mediating developmental angiogenesis and vascular permeability [ research paper 03/79 ]. Recent new evidence gathered so far has indicated that VEGF plays a multifunctional role where it can also have autocrine pro-survival effects and lead to tumor cell ross 2009 essays. Targeting angiogenesis and VEGF receptors essay about the street children clinically important implications for optimizing the chemotherapy research paper 03/79 [ 44 ].
Recent studies have demonstrated chemokine as an important determinant of cancer cell sensitivity to chemotherapy [ 45 ]. In the network, act vs rule utilitarianism essay miRNAs along with 31 target mRNAs constructed the prediction framework including 66 regulatory pairs Figure 7. The identified miRNAs and target mRNAs have been proved highly associated with docetaxel resistance by integrative functional analysis and verification in literatures and essay starting sentence provide potential miRNA-mRNA regulatory thesis statements for hamlet on revenge as network biomarkers for prediction online essay about kojiki docetaxel research paper 03/79.