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  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 22 ( 2022-11-10), p. 13873-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 22 ( 2022-11-10), p. 13873-
    Abstract: To evaluate the role of ubiquitin-conjugating enzyme E2C (UBE2C) in prostate cancer (PCa) progression and prognosis, the TCGA and our PCa tissue microarray cohort were included in the study. Weighted gene co-expression network analysis (WGCNA) and non-negative matrix factorization were used to cluster patients and to screen genes that play a vital role in PCa progression (hub gene). Immunohistochemistry staining was used to evaluate the protein level of UBE2C in prostatic tissues. Through WGCNA, we found a gene co-expression module (named the purple module) that is strongly associated with the Gleason score, pathologic T stage, and biochemical recurrent status. Genes in the purple module are enriched in cell cycle and P53 signaling and help us to cluster patients into two groups with distinctive biochemical recurrent survival rates and TP53 mutation statuses. Further analysis showed UBE2C served as a hub gene in the purple module. The expression of UBE2C in PCa was significantly higher than that in paracancerous tissues and was remarkably associated with pathologic grade, Gleason score, and prognosis in PCa patients. To conclude, UBE2C is a PCa-progress-related gene and a biomarker for PCa patients. Therapy targeting UBE2C may serve as a promising treatment of PCa in the future.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 5 ( 2022-03-02), p. 2770-
    Abstract: Glioblastoma is the most aggressive brain tumour with short survival, partly due to resistance to conventional therapy. Glioma stem cells (GSC) are likely to be involved in treatment resistance, by releasing extracellular vesicles (EVs) containing specific molecular cargoes. Here, we studied the EVs secreted by glioma stem cells (GSC-EVs) and their effects on radiation resistance and glioma progression. EVs were isolated from 3 GSCs by serial centrifugation. NanoSight measurement, cryo-electron microscopy and live imaging were used to study the EVs size, morphology and uptake, respectively. The non-GSC glioma cell lines LN229 and U118 were utilised as a recipient cell model. Wound healing assays were performed to detect cell migration. Colony formation, cell viability and invadopodium assays were conducted to detect cell survival of irradiated recipient cells and cell invasion post GSC-EV treatment. NanoString miRNA global profiling was used to select for the GSC-EVs’ specific miRNAs. All three GSC cell lines secreted different amounts of EVs, and all expressed consistent levels of CD9 but different level of Alix, TSG101 and CD81. EVs were taken up by both LN229 and U118 recipient cells. In the presence of GSC-EVs, these recipient cells survived radiation exposure and initiated colony formation. After GSC-EVs exposure, LN229 and U118 cells exhibited an invasive phenotype, as indicated by an increase in cell migration. We also identified 25 highly expressed miRNAs in the GSC-EVs examined, and 8 of these miRNAs can target PTEN. It is likely that GSC-EVs and their specific miRNAs induced the phenotypic changes in the recipient cells due to the activation of the PTEN/Akt pathway. This study demonstrated that GSC-EVs have the potential to induce radiation resistance and modulate the tumour microenvironment to promote glioma progression. Future therapeutic studies should be designed to interfere with these GSC-EVs and their specific miRNAs.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 16 ( 2022-08-21), p. 4035-
    In: Cancers, MDPI AG, Vol. 14, No. 16 ( 2022-08-21), p. 4035-
    Abstract: Prostate cancer (PCa) is one of the most common cancers in men. Usually, most PCas at initial diagnosis are localized and hormone-dependent, and grow slowly. Patients with localized PCas have a nearly 100% 5-year survival rate; however, the 5-year survival rate of metastatic or progressive PCa is still dismal. N6-methyladenosine (m6A) is the most common post-transcriptional mRNA modification and is dynamically regulated by m6A regulators. A few studies have shown that the abnormal expression of m6A regulators is significantly associated with cancer progression and immune cell infiltration, but the roles of these regulators in PCa remain unclear. Here, we examined the expression profiles and methylation levels of 21 m6A regulators across the Cancer Genome Atlas (TCGA), 495 PCas by consensus clustering, and correlated the expression of m6A regulators with PCa progression and immune cell infiltration. Consensus clustering was applied for subtyping Pca samples into clusters based on the expression profiles of m6A regulators. Each subtype’s signature genes were obtained by a pairwise differential expression analysis. Featured pathways of m6A subtypes were predicted by Gene Ontology. The m6A score was developed to predict m6A activation. The association of the m6A score with patients’ survival, metastasis and immune cell infiltration was also investigated. We identified three distinct clusters in PCa based on the expression profiles of 21 m6A regulators by consensus clustering. The differential expression and pathway analyses on the three clusters uncovered the m6A regulators involved in metabolic processes and immune responses in PCa. Moreover, we developed an m6A score to evaluate the m6A regulator activation for PCa. The m6A score is significantly associated with Gleason scores and metastasis in PCa. The predictive capacity of the m6A score on PCa metastasis was also validated in another independent cohort with an area under the curve of 89.5%. Hence, our study revealed the critical role of m6A regulators in PCa progression and the m6A score is a promising predictive biomarker for PCa metastasis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 4
    In: Micromachines, MDPI AG, Vol. 12, No. 4 ( 2021-03-30), p. 369-
    Abstract: As an excellent multifunctional single crystal, potassium dihydrogen phosphate (KDP) is a well-known, difficult-to-process material for its soft-brittle and deliquescent nature. The surface mechanical properties are critical to the machining process; however, the characteristics of deformation behavior for KDP crystals have not been well studied. In this work, the strain rate effect on hardness was investigated on the mechanically polished tripler plane of a KDP crystal relying on nanoindentation technology. By increasing the strain rate from 0.001 to 0.1 s−1, hardness increased from 1.67 to 2.07 GPa. Hence, the strain rate sensitivity was determined as 0.053, and the activation volume of dislocation nucleation was 169 Å3. Based on the constant load-holding method, creep deformation was studied at various holding depths at room temperature. Under the spherical tip, creep deformation could be greatly enhanced with increasing holding depth, which was mainly due to the enlarged holding strain. Under the self-similar Berkovich indenter, creep strain could be reduced at a deeper location. Such an indentation size effect on creep deformation was firstly reported for KDP crystals. The strain rate sensitivity of the steady-state creep flow was estimated, and the creep mechanism was qualitatively discussed.
    Type of Medium: Online Resource
    ISSN: 2072-666X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2620864-7
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  • 5
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 11 ( 2019-05-29), p. 2643-
    Abstract: Clinopodium chinense (Benth.) O. Kuntze (C. chinense) is an important herb in traditional Chinese medicine. Triterpenoid saponins are a major class of active compounds in C. chinense with broad pharmacological activities and hemostatic, antitumor, and anti-hyperglycemic effects. To identify genes involved in triterpenoid saponin biosynthesis, transcriptomic analyses of leaves, stems, and roots from C. chinense were performed. A total of 135,968 unigenes were obtained by assembling the leaf, stem, and root transcripts, of which 102,154 were annotated in public databases. Differentially expressed genes were determined based on expression profile analysis and analyzed for differential expression of unique genes related to triterpenoid saponin biosynthesis. Multiple unigenes encoding crucial enzymes or transcription factors involved in triterpenoid saponin synthesis were identified and analyzed. The expression levels of unigenes encoding enzymes were experimentally validated using quantitative real-time PCR. This study greatly broadens the public transcriptome database for this species and provides a valuable resource for identifying candidate genes involved in the biosynthesis of triterpenoid saponins and other secondary metabolites.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 5 ( 2021-03-05), p. 1113-
    In: Cancers, MDPI AG, Vol. 13, No. 5 ( 2021-03-05), p. 1113-
    Abstract: Meningioma is the most common tumor in central nervous system (CNS). Although most cases of meningioma are benign (WHO grade I) and curable by surgical resection, a few tumors remain diagnostically and therapeutically challenging due to the frequent recurrence and progression. The heterogeneity of meningioma revealed by DNA methylation profiling suggests the demand of subtyping for meningioma. Therefore, we performed a clustering analyses to characterize the progressive features of meningioma and constructed a meningioma progression score to predict the risk of the recurrence. A total of 179 meningioma transcriptome from RNA sequencing was included for progression subtype clustering. Four biologically distinct subtypes (subtype 1, subtype 2, subtype 3 and subtype 4) were identified. Copy number alternation and genomewide DNA methylation of each subtype was also characterized. Immune cell infiltration was examined by the microenvironment cell populations counter. All anaplastic meningiomas (7/7) and most atypical meningiomas (24/32) are enriched in subtype 3 while no WHO II or III meningioma presents in subtype 1, suggesting subtype 3 meningioma is a progressive subtype. Stemness index and immune response are also heterogeneous across four subtypes. Monocytic lineage is the most immune cell type in all meningiomas, except for subtype 1. CD8 positive T cells are predominantly observed in subtype 3. To extend the clinical utility of progressive meningioma subtyping, we constructed the meningioma progression score (MPscore) by the signature genes in subtype 3. The predictive accuracy and prognostic capacity of MPscore has also been validated in three independent cohort. Our study uncovers four biologically distinct subtypes in meningioma and the MPscore is potentially helpful in the recurrence risk prediction and response to treatments stratification in meningioma.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
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