RESUMO
BACKGROUND: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. METHODS: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. RESULTS: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1α (HIF-1α), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. CONCLUSIONS: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.
Assuntos
Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos/genética , Neoplasias/genética , Regiões Promotoras Genéticas , Animais , Linhagem Celular Tumoral , Biologia Computacional/métodos , Expressão Gênica , Perfilação da Expressão Gênica , Genes Reporter , Humanos , Camundongos , Camundongos Transgênicos , Neoplasias/metabolismo , Ligação Proteica , Mapeamento de Interação de Proteínas , Fatores de Transcrição/metabolismo , TransgenesRESUMO
MicroRNAs (miRNAs) are small non-coding RNAs of â¼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased â¼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.
Assuntos
Bases de Dados Genéticas , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Mineração de Dados , Humanos , RNA Mensageiro/química , Interface Usuário-ComputadorRESUMO
The purpose of the study was to investigate the effects of research-article writing motivation and use of self-regulatory writing strategies in explaining second language (L2) research-article abstract writing ability, alongside the L2 literacy effect. Four measures were administered: a L2 literacy test, a research abstract performance assessment, and inventories of writing motivation and strategy. Participants were L2 graduate students in Taiwan (N=185; M age=25.8 yr., SD=4.5, range=22-53). Results of structural equation modeling showed a direct effect of motivation on research-article writing ability, but no direct effect of strategy or indirect effect of motivation via strategy on research-article writing ability, with L2 literacy controlled. The findings suggest research-article writing instruction should address writing motivation, besides L2 literacy.
Assuntos
Linguística , Motivação , Multilinguismo , Pesquisa , Redação , Adulto , Feminino , Humanos , Masculino , Taiwan , Adulto JovemRESUMO
This study investigates the progression of family cohesion perceptions and depressive symptoms during the character development stage in adolescents. Data were used from the Taiwan Youth Project. The final sample comprised 2,690 adolescents with 1,312 girls (48.8%; M age = 13.0 yr., SD = 0.5). Latent curve growth analysis was employed to explore these developments. Seventh-grade girls reported greater family cohesion and more depressive symptoms than boys, and boys reported greater growth in family cohesion than girls. However, progression of depressive symptoms was not associated with the child's sex. Higher perceived family cohesion in Grade 7 correlated with less increase of depressive symptoms from Grades 9 to 11. The long-term positive influence of family cohesion on depressive symptoms is discussed.
Assuntos
Depressão/epidemiologia , Relações Familiares , Percepção Social , Adolescente , Depressão/psicologia , Família/psicologia , Feminino , Identidade de Gênero , Humanos , Estudos Longitudinais , Masculino , Distribuição por Sexo , Taiwan/epidemiologiaRESUMO
This study aims to assess the measurement invariance of the three subscales of the newly developed Academic Performance Antecedent Scale (APAS)--School Factors, Mother's Parenting Style, and Individual Factors--across native and new immigrant children in Taiwan. The study sample comprised 527 Grade 4 students (M age = 10.4 yr., SD = 0.6), 263 boys and 264 girls. The three groups were urban and rural children of Taiwanese natives (n = 343, 65.1%), and 184 children with non-Taiwanese mothers (34.9%). The four-factor structure of the School Factors Subscale, the three-factor structure of the Mother's Parenting Style Subscale, and the five-factor structure of the Individual Factors Subscale all showed at least acceptable fit for the groups. In addition, metric invariance was confirmed for the School Factors and Individual Factors Subscales. Metric invariance was partially obtained for the Mother's Parenting Style Subscale. The findings provide validity evidences for cross-cultural generalizability of the APAS.