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Item type:Item, MicroRNAs and Apoptosis in Colorectal Cancer(2020-08-01) ;Wang, Hsiuying ;統計學研究所Institute of StatisticsColorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is rising in developing countries. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, de-regulated apoptotic signaling allows cancer cells to escape this signaling, leading to therapeutic resistance. Treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells.Item type:Item, Anti-NMDA Receptor Encephalitis: Efficacy of Treatment for Male Patients and miRNA Biomarker(2020-01-01) ;Wang, Hsiuying ;統計學研究所Institute of StatisticsBackground: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an acute form of encephalitis. Treatments for the anti-NMDA receptor encephalitis usually include steroids, intravenous immunoglobulin, plasma exchange, plasmapheresis, rituximab, cyclophosphamide and tumor resection. Objective: We aimed to compare the efficacy of the treatments including intravenous immunoglobulin, plasma exchange, plasmapheresis, rituximab or cyclophosphamide for male anti- NMDA receptor encephalitis patients without tumor and to discuss potential biomarkers for this disease. Method: The Fisher exact test and the contingency table analysis were used to analyze the treatment efficacy for 43 male and 76 female patients. In addition, a hierarchical tree method was adopted to analyze the difference in the treatment efficacy between male and female patients. Results: The p-values of testing whether the efficacy rate of plasmapheresis (or plasma exchange) for the male patient is greater than a threshold are significantly different from the p-values for the other two treatments. In addition, the hierarchical tree method shows that the treatment strategy associating with early recovery is different for male and female patients. Conclusion: The results revealed that the efficacy rate of plasmapheresis (or plasma exchange) is not inferior to that of intravenous immunoglobulin and rituximab (or cyclophosphamide) for male patients without tumor. In addition, B-cell attracting C-X-C motif chemokine 13 (CXCL13) and microRNA let-7b have the potential to be the treatment response biomarkers for anti-NMDA receptor encephalitis. They may not be useful prognostic biomarkers for this encephalitis unless they are not biomarkers for other autoimmune encephalitides.Item type:Item, Phylogenetic Analysis to Explore the Association Between Anti-NMDA Receptor Encephalitis and Tumors Based on microRNA Biomarkers(2019-10-01) ;Wang, Hsiuying ;統計學研究所Institute of StatisticsMicroRNA (miRNA) is a small non-coding RNA that functions in the epigenetics control of gene expression, which can be used as a useful biomarker for diseases. Anti-NMDA receptor (anti-NMDAR) encephalitis is an acute autoimmune disorder. Some patients have been found to have tumors, specifically teratomas. This disease occurs more often in females than in males. Most of them have a significant recovery after tumor resection, which shows that the tumor may induce anti-NMDAR encephalitis. In this study, I review microRNA (miRNA) biomarkers that are associated with anti-NMDAR encephalitis and related tumors, respectively. To the best of my knowledge, there has not been any research in the literature investigating the relationship between anti-NMDAR encephalitis and tumors through their miRNA biomarkers. I adopt a phylogenetic analysis to plot the phylogenetic trees of their miRNA biomarkers. From the analyzed results, it may be concluded that (i) there is a relationship between these tumors and anti-NMDAR encephalitis, and (ii) this disease occurs more often in females than in males. This sheds light on this issue through miRNA intervention.Item type:Item, Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis(2015-01-01) ;Chen, Feng-Chi ;生物科技學系Department of Biological Science and TechnologyAlternative RNA structures (ARSs), or alternative transcript isoforms, are critical for regulating cellular phenotypes in humans. In addition to generating functionally diverse protein isoforms from a single gene, ARS can alter the sequence contents of 5'/3' untranslated regions (UTRs) and intronic regions, thus also affecting the regulatory effects of these regions. ARS may introduce premature stop codon(s) into a transcript, and render the transcript susceptible to nonsense-mediated decay, which in turn can influence the overall gene expression level. Meanwhile, ARS can regulate the presence/absence of upstream open reading frames and microRNA targeting sites in 5'UTRs and 3'UTRs, respectively, thus affecting translational efficiencies and protein expression levels. Furthermore, since ARS may alter exon-intron structures, it can influence the biogenesis of intronic microRNAs and indirectly affect the expression of the target genes of these microRNAs. The connections between ARS and multiple regulatory mechanisms underline the importance of ARS in determining cell fate. Accumulating evidence indicates that ARS-coupled regulations play important roles in tumorigenesis. Here I will review our current knowledge in this field, and discuss potential future directions.Item type:Item, Predicting MicroRNA Biomarkers for Cancer Using Phylogenetic Tree and Microarray Analysis(2016-05-01) ;Wang, Hsiuying ;統計學研究所Institute of StatisticsMicroRNAs (miRNAs) are shown to be involved in the initiation and progression of cancers in the literature, and the expression of miRNAs is used as an important cancer prognostic tool. The aim of this study is to predict high-confidence miRNA biomarkers for cancer. We adopt a method that combines miRNA phylogenetic structure and miRNA microarray data analysis to discover high-confidence miRNA biomarkers for colon, prostate, pancreatic, lung, breast, bladder and kidney cancers. There are 53 miRNAs selected through this method that either have potential to involve a single cancer's development or to involve several cancers' development. These miRNAs can be used as high-confidence miRNA biomarkers of these seven investigated cancers for further experiment validation. miR-17, miR-20, miR-106a, miR-106b, miR-92, miR-25, miR-16, miR-195 and miR-143 are selected to involve a single cancer's development in these seven cancers. They have the potential to be useful miRNA biomarkers when the result can be confirmed by experiments.Item type:Item, Anti-NMDA Receptor Encephalitis and Vaccination(2017-01-01) ;Wang, Hsiuying ;統計學研究所Institute of StatisticsAnti-N-methyl-D-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.Item type:Item, Exploring MicroRNA Biomarkers for Parkinson's Disease from mRNA Expression Profiles(2018-12-01) ;Taguchi, Y-h ;Wang, Hsiuying ;統計學研究所Institute of StatisticsParkinson's disease (PD) is a chronic, progressive neurodegenerative disease characterized by both motor and nonmotor features. The diagnose of PD is based on a review of patients' signs and symptoms, and neurological and physical examinations. So far, no tests have been devised that can conclusively diagnose PD. In this study, we explore both microRNA and gene biomarkers for PD. Microarray gene expression profiles for PD patients and healthy control are analyzed using a principal component analysis (PCA)-based unsupervised feature extraction (FE). 244 genes are selected to be potential gene biomarkers for PD. In addition, we implement these genes into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and find that the 15 microRNAs (miRNAs), hsa-miR-92a-3p, 16-5p, 615-3p, 877-3p, 100-5p, 320a, 877-5p, 23a-3p, 484, 23b-3p, 15a-5p, 324-3p, 19b-3p, 7b-5p and 505-3p, significantly target these 244 genes. These miRNAs are shown to be significantly related to PD. This reveals that both selected genes and miRNAs are potential biomarkers for PD.Item type:Item, Multifunctional silver nanocluster-hybrid oligonucleotide vehicle for cell imaging and microRNA-targeted gene silencing(2017-04-01) ;Chen, Hau-Yun ;Albert, Karunya ;Wen, Cheng-Che ;Hsieh, Pei-YingChen, Sih-YuNovel therapeutics is urgently needed to prevent cancer-related deaths. MicroRNAs that act as tumor suppressors have been recognized as a next-generation tumor therapy, and the restoration of tumor suppressive microRNAs using microRNA replacements or mimics may be a less toxic, more effective strategy due to fewer off-target effects. Here, we designed the novel multifunctional oligonucleotide nanocarrier complex composed of a tumor-targeting aptamer sequence specific to mucin 1. (MUC1), poly-cytosine region for fluorescent silver nanocluster (AgNC) synthesis, and complimentary sequence for microRNA miR-34a loading. MiR-34a was employed because of its therapeutic effect of inhibiting oncogene expression and inducing apoptosis in carcinomas. By monitoring the intrinsic fluorescence of AgNC, it was clearly shown that the constructed complex (MUC1-AgNCm-miR-34a) enters MCF-7 cells. To evaluate the efficacy of this nanocarrier for microRNA delivery, we investigated the gene and protein expression levels of downstream miR-34a targets (BCL-2, CDK6, and CCNDI) by quantitative PCR and western blotting, respectively, and the results indicated their effective inhibition by miR-34a. This novel multifunctional AgNC-based nanocarrier can aid in improving the efficacy of breast cancer theranostics. (C) 2017 Elsevier B.V. All rights reserved.Item type:Item, Integrated microRNA and mRNA expression profile analysis of tumor-associated macrophages after exposure to single-dose irradiation(2018-06-01) ;Kung, Wei-Hsiang ;Lee, Chi-Lung ;Yang, Chi-Dung ;Yu, Ching-FangChiew, Men-YeeBackground: Radiotherapy (RT) is a common approach that accounts for nearly 50% of cancer patient treatment and has the potential for long-term tumor control Recently, we published a research article on gene expression profiling of tumor-associated macrophages (TAM) that were exposed to ionizing radiation (IR). Single-dose irradiation of tumors could initiate differentially expressed genes in TAM as a time series from irradiated tumors that are associated with the immune response. It is also well known that human cancers are associated with microRNA (miRNA) alterations that are involved in cancer progression. However, the role of miRNA on TAM after exposure to irradiation remains unclear. Results: In this study, miRNA expression profiles from microarrays were used to identify the key miRNAs and correlating pathways involved in the role of TAMs in tumor progression and recurrence after RT. Using a mouse tumor model, we identified miRNA pattern changes over time in response to irradiation. Based on our results, we hypothesize that miRNA expression in the irradiated tumor may be used as a distinguishing marker to indicate the best time for therapeutic intervention to prevent tumor recurrence after RT. Conclusions: We established a murine model irradiated with a single dose of 25 Gy that could initiate temporal changes in the expression of miRNAs associated with cell proliferation and the immune response, as evidenced by macrophages directly extracted from irradiated tumors after two weeks of IR. Statistical analyses were conducted by comparing the miRNA expression in macrophages from non-lrradiated versus irradiated tumors. Thus, our study could lead to a better understanding of the function of miRNA expressions, which changed temporally in an irradiated tumor microenvironment. (C) 2018 Elsevier Ltd. All rights reserved.Item type:Item, Exploring microRNA Biomarker for Amyotrophic Lateral Sclerosis(2018-05-01) ;Taguchi, Y-h. ;Wang, Hsiuying ;統計學研究所Institute of StatisticsAmyotrophic lateral sclerosis (ALS) is among the severe neuro degenerative diseases that lack widely available effective treatments. As the disease progresses, patients lose the control of voluntary muscles. Although the neuronal degeneration is the cause of this disease, the failure mechanism is still unknown. In order to seek genetic mechanisms that initiate and progress ALS, the association of microRNA (miRNA) expression with this disease was considered. Serum miRNAs from healthy controls, sporadic ALS (sALS), familial ALS (fALS) and ALS mutation carriers were investigated. Principal component analysis (PCA)-based unsupervised feature extraction (FE) was applied to these serum miRNA profiles. As a result, we predict miRNAs that can discriminate patients from healthy controls with high accuracy. Thus, these miRNAs can be potential prognosis miRNA biomarkers for ALS.