MiR-30a-5p overexpression may overcome EGFR-inhibitor resistance through regulating PI3K/AKT signalling pathway in Non-Small Cell Lung Cancer cell lines

Lung cancer is one of the most common deadly diseases worldwide, most of which is non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutant NSCLCs frequently respond to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) treatment, such as Gefitinib and Erlotinib, but the development of acquired resistance limits the utility. Multiple resistance mechanisms have been explored, e.g. the activation of alternative tyrosine kinase receptors (TKRs) sharing similar downstream pathways to EGFR. MicroRNAs (MiRNAs) are short, endogenous and non-coding RNA molecules, regulating the target gene expression. In this study, we explored the potential of miR-30a-5p in targeting the EGFR and insulin-like growth factor receptor-1 (IGF-1R) signalling pathways to overcome the drug resistance. IGF-1R is one of the tyrosine kinase receptors that share the same EGFR downstream molecules, including phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT). In this work, an in vitro study was designed using EGFR inhibitor (Gefitinib), IGF-1R inhibitor (NVP-AEW541), and miRNA mimics in two Gefitinib-resistant NSCLC cell lines, H460 and H1975. We found that the combination of EGFR and IGF-1R inhibitors significantly decreased the phosphorylated AKT (p-AKT) expression levels compared to the control group in these two cell lines. Knockdown of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) had the same effect with the dual inhibition of EGFR and IGF-1R to reduce the expression of p-AKT in the signalling pathway. Overexpression of miR-30a-5p significantly reduced the expression of the PI3K regulatory subunit (PIK3R2) to further induce cell apoptosis, and inhibit cell invasion and migration properties. Hence, miR-30a-5p may play vital roles in overcoming the acquired resistance to EGFR-TKIs, and provide useful information for establishing novel cancer treatment

Solar-blind ultraviolet photodetector based on graphene/vertical Ga2O3 nanowire array heterojunction

In this paper, a solar-blind ultraviolet photodetector (PD) based on the graphene/vertical Ga2O3 nanowire array heterojunction was proposed and demonstrated. To the best of our knowledge, it is the first time that vertical Ga2O3 nanowire arrays have been realized. Ga2O3 nanowires were obtained by thermally oxidizing GaN nanowires grown by molecular beam epitaxy on n-doped Si substrate. Then, a monolayer graphene film was transferred to Ga2O3 nanowires to form the graphene/vertical Ga2O3 nanowire array heterojunction and transparent electrodes. The fabricated device exhibited a responsivity (R) of 0.185 A/W and rejection ratio (R258 nm/R365 nm) of 3×104 at the bias of −5 V. Moreover, the fast response times of this PD were 9 and 8 ms for the rise and decay times under 254 nm illumination, respectively, which are attributed to the unique properties of nanowire arrays and the graphene/vertical Ga2O3 nanowire array heterojunction structure

Computational Characterization of Undifferentially Expressed Genes with Altered Transcription Regulation in Lung Cancer.

Peer reviewed: TrueAcknowledgements: We extend our sincere thanks to the two anonymous reviewers for their insightful and constructive critiques. Their expert evaluations have significantly contributed to the improvement of our manuscript, notably, in refining the clarity, enhancing the visual presentation, and strengthening the argumentative rigor of our work.Publication status: PublishedFunder: Fundamental Research Funds for the Central UniversitiesA transcriptome profiles the expression levels of genes in cells and has accumulated a huge amount of public data. Most of the existing biomarker-related studies investigated the differential expression of individual transcriptomic features under the assumption of inter-feature independence. Many transcriptomic features without differential expression were ignored from the biomarker lists. This study proposed a computational analysis protocol (mqTrans) to analyze transcriptomes from the view of high-dimensional inter-feature correlations. The mqTrans protocol trained a regression model to predict the expression of an mRNA feature from those of the transcription factors (TFs). The difference between the predicted and real expression of an mRNA feature in a query sample was defined as the mqTrans feature. The new mqTrans view facilitated the detection of thirteen transcriptomic features with differentially expressed mqTrans features, but without differential expression in the original transcriptomic values in three independent datasets of lung cancer. These features were called dark biomarkers because they would have been ignored in a conventional differential analysis. The detailed discussion of one dark biomarker, GBP5, and additional validation experiments suggested that the overlapping long non-coding RNAs might have contributed to this interesting phenomenon. In summary, this study aimed to find undifferentially expressed genes with significantly changed mqTrans values in lung cancer. These genes were usually ignored in most biomarker detection studies of undifferential expression. However, their differentially expressed mqTrans values in three independent datasets suggested their strong associations with lung cancer

Disease-Specific Target Gene Expression Profiling of Molecular Imaging Probes: Database Development and Clinical Validation

Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2- deoxy-2-D-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/

Genome Sequence of the Anaerobic, Thermophilic, and Cellulolytic Bacterium “Anaerocellum thermophilum” DSM 6725▿

“Anaerocellum thermophilum” DSM 6725 is a strictly anaerobic bacterium that grows optimally at 75°C. It uses a variety of polysaccharides, including crystalline cellulose and untreated plant biomass, and has potential utility in biomass conversion. Here we report its complete genome sequence of 2.97 Mb, which is contained within one chromosome and two plasmids (of 8.3 and 3.6 kb). The genome encodes a broad set of cellulolytic enzymes, transporters, and pathways for sugar utilization and compared to those of other saccharolytic, anaerobic thermophiles is most similar to that of Caldicellulosiruptor saccharolyticus DSM 8903