ABSTRACT
OBJECTIVE: We attempt to investigate the biological function of the discoidin, complement C1r/C1s,Uegf, and Bmp1 and Limulus factor C, Coch, and Lgl domain-containing 2 (DCBLD2) in glioblastoma, as well as its effect on the epithelial-mesenchymal transition (EMT) process. METHODS: The public expression data of glioblastoma samples and normal brain samples from The Cancer Genome Atlas database, Genotype-Tissue Expression database and Chinese Glioma Genome Atlas database were used to analyze the expression of DCBLD2 and its relationship with the survival of patients with glioblastoma. Quantitative real-time PCR and western blot were used to evaluate mRNA and protein levels of DCBLD2. Cell viabilities were tested using Cell Counting Kit-8 and clone formation assays. Cell invasive and migratory abilities were measured by transwell assays. RESULTS: DCBLD2 expression was upregulated in glioblastoma and has a significantly positive correlation with the WHO classification. In addition, high expression of DCBLD2 was closely correlated with poor prognosis in primary and recurrent patients with glioblastoma. What is more, we found that knockdown of DCBLD2 notably reduced the cell proliferative, invasive and migratory capacities by elevating the expression of E-cadherin and inhibiting the expression of vimentin, snail, slug and twist. However, overexpression of DCBLD2 presented the opposite results. CONCLUSION: The current study reveals that high expression of DCBLD2 is closely related to poor prognosis in glioblastoma and can significantly enhance the tumor cell viability and metastasis by activating the EMT process, suggesting that DCBLD2 may be a possible biomarker for glioblastoma treatment.
Subject(s)
Brain Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , Glioblastoma/genetics , Membrane Proteins/genetics , Antigens, CD/genetics , Antigens, CD/metabolism , Blotting, Western , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cadherins/genetics , Cadherins/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Databases, Genetic , Gene Knockdown Techniques , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Membrane Proteins/metabolism , Neoplasm Invasiveness , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Prognosis , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolism , Survival Rate , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism , Up-Regulation , Vimentin/genetics , Vimentin/metabolismABSTRACT
This study attempted to research the molecular mechanism underlying the inhibitory role of miR-1225-5p in the malignant progression of glioblastoma. Bioinformatics analyses based on the gene expression omnibus (GEO) and Chinese glioma genome atlas (CGGA) databases showed that miR-1225-5p, as a favorable prognostic factor, was expressed at low levels in glioblastoma, and its expression was also related to WHO grade and age. The subsequent CCK-8 assay indicated that miR-1225-5p might prevent the malignant progression of glioblastoma, which was represented by that miR-1225-5p mimic reduced the viability of glioblastoma cells. Then, we predicted that FNDC3B might be a potential target gene of miR-1225-5p, and it was negatively correlated with the level of miR-1225-5p, which were confirmed by dual-luciferase reporter assay, qRT-PCR and western blot assays. Moreover, based on the analyses of the cancer genome atlas (TCGA), Oncomine and CGGA databases, FNDC3B was enriched in glioblastoma and high expression of FNDC3B led to poor prognosis. Finally, CCK8 and transwell experiments showed that the ability of miR-1225-5p to inhibit glioblastoma cell viability, invasion and migration was at least partially achieved by targeting FNDC3B. In general, these results revealed that the miR-1225-5p/FNDC3B axis contributes to inhibiting the malignant phenotype of glioblastoma cells, which lays a foundation for molecular diagnosis and treatment of glioblastoma.
ABSTRACT
Primary and acquired drug resistance is one of the main obstacles encountered in high-grade serous ovarian cancer (HGSC) chemotherapy. Cisplatin induces DNA damage through cross-linking and long integrated non-coding RNAs (lincRNAs) play an important role in chemical induced DNA-damage response, which suggests that lincRNAs may be also associated with cisplatin resistance. However, the mechanism of long integrated non-coding RNAs (lincRNAs) acting on cisplatin resistance is not well understood. Here, we showed that expression of lin-RECK-3, H19, LUCAT1, LINC00961, and linc-CARS2-2 was enhanced in cisplatin-resistant A2780-DR cells, while transcriptome sequencing showed decreased Linc-TNFRSF19-1 and LINC00515 expression. Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.
Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Glutathione/metabolism , Neoplasms, Cystic, Mucinous, and Serous/pathology , Ovarian Neoplasms/pathology , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Female , Gene Expression Profiling , HumansABSTRACT
Evaluating the frost-resistance of evergreen woody plants is of significance in guiding the species selection in forest management in subtropical region. In this paper, an investigation was made on the functional traits (including specific leaf area, stem wood density, leaf area, leaf dry matter content, leaf relative electrical conductance, and twig wood density) of 64 common evergreen broad-leaved and coniferous woody plant species in the Ningbo region of Zhejiang Province, East China, after a severe snowstorm in early 2008, aimed to select the evergreen woody plants with high ability of freeze-tolerance, and to establish a related evaluation system. By using a hierarchy analysis approach, the weight values of the functional traits of each species were determined, and an index system for evaluating the plants tolerance ability against freeze and mechanical damage was established. Based on this system, 23 evergreen plant species with high tolerance ability against freeze and mechanical damage, such as Cyclobalanopsis gilva, Cyclobalanopsis nubium, Neolitsea aurata, and Vacciniuim mandarinorum, were selected. In the meantime, on the basis of the ordering with each of the functional traits, the ordering of the tolerance ability of the 64 plant species against freeze and mechanical damage was made, and a list for the frost-resistance ability of the subtropical evergreen woody plant species in Ningbo region was constituted.
