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OBJECTIVE: Skin basal cell carcinoma (BCC) is the most common malignant skin tumor. Recent studies demonstrated that circular RNAs (circRNAs) are implicated in tumorigenesis and may represent potential therapeutic targets. The aim of the present study was to explore the expression profiles of circRNAs and their role in skin BCC. MATERIALS AND METHODS: Three pairs of skin BCC tissues and adjacent tissues were used to perform a circRNA microarray for screening of circRNA expression profiles. Circ_NCKAP1 was selected as a target circRNA by RT-qPCR verification and bioinformatics analysis. The effect of circ_NCKAP1 knockdown on cell proliferation and apoptosis was assessed using CCK8 and Annexin V-FITC/PI assays, and its regulation over the miR-148b-5p/HSP90 axis was assessed by dual-luciferase reporter assay. RESULTS: Circ_NCKAP1 was found to be significantly upregulated in skin BCC tissues (p<0.05). In vitro loss-of-function assays demonstrated that circ_NCKAP1 knockdown markedly inhibited cell proliferation and promoted cell apoptosis (p<0.05). Moreover, Dual-Luciferase reporter assay identified that circ_NCKAP1 could bind to miR-148b-5p directly, and HSP90 was targeted by miR-148b-5p. CONCLUSIONS: Circ_NCKAP1 can promote skin BCC progression by sponging the miR-148b-5p/HSP90 axis, and circ_NCKAP1 may be a potential target for skin BCC therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Despite many studies on the biogenesis, molecular structure and biological functions of microRNAs, little is known about the transcriptional regulatory mechanisms controlling the spatiotemporal expression pattern of human miRNA gene loci. Several lines of experimental results have indicated that both polymerase II (Pol-II) and polymerase III (Pol-III) may be involved in transcribing miRNAs. Here, we assessed the genomic evidence for Alu-directed transcriptional regulation of some novel miRNA genes in humans. Our data demonstrate that the expression of these Alu-related miRNAs may be modulated by Pol-III. Results We present a comprehensive exploration of the Alu-directed transcriptional regulation of some new miRNAs. Using a new computational approach, a variety of Alu-related sequences from multiple sources were pooled and filtered to obtain a subset containing Alu elements and characterized miRNA genes for which there is clear evidence of full-length transcription (embedded in EST). We systematically demonstrated that 73 miRNAs including five known ones may be transcribed by Pol-III through Alu or MIR. Among the new miRNAs, 33 were determined by high-throughput Solexa sequencing. Real-time TaqMan PCR and Northern blotting verified that three newly identified miRNAs could be induced to co-express with their upstream Alu transcripts by heat shock or cycloheximide. Conclusion Through genomic analysis, Solexa sequencing and experimental validation, we have identified candidate sequences for Alu-related miRNAs, and have found that the transcription of these miRNAs could be governed by Pol-III. Thus, this study may elucidate the mechanisms by which the expression of a class of small RNAs may be regulated by their upstream repeat elements.

Liuwei Dihuang decoction (LWDH) has been used to treat age-related diseases in Asia for thousands of years. Its effect is significant, but the mechanism is not entirely understood. The development and maturity of metabonomics technology have created a new way to understand its effects. In this study, 20-month-old naturally aging mice were used as the research subjects. Mice were randomly divided into the young group, elderly group, vitamin E group, and LWDH group, with 10 mice in each group. The UPLC-Q-TOF-MS technique analyzed the changes in plasma metabolism of these mice. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to study metabolic markers and metabolic pathways. Compared with the elderly group, the organ index and weight-bearing swimming time of the LWDH and vitamin E groups increased (P ≤ 0.01). The results show that LWDH can benignly regulate the expression level of 11 aging-associated metabolites in aged mice and alleviate the aging state of mice. These metabolites mainly affect the metabolism of glutathione, unsaturated fatty acid biosynthesis, pyrimidine, selenium, pentose phosphate, arginine, and proline. [ABSTRACT FROM AUTHOR]

We discuss the growth function of a finitely generated cascade and its connection to the growth function of its related semi-direct product (Conjecture 1.9). The results is applied for simpler proof of well-known results in the realm of geometric group theory. We show that the finitely generated cascades on nilpotent groups obey the dichotomy rule (only polynomial and exponential growth are possible). [ABSTRACT FROM AUTHOR]

The selection of appropriate parameter combinations of laser cladding is crucial to obtain desirable quality of cladding layer. In this study a fractional factorial design with fraction of 1/6 experiment is implemented, and main laser cladding parameters including laser power, scanning speed and feeding rate are selected to analyse the impact on geometrical shapes (including clad width, clad height and clad depth) of cladding layer. Integrating entropy method, the technique for order of preference by similarity to ideal solution (TOPSIS) is employed here to optimize and find appropriate parameter combination to realize the desirable clad quality with large clad width, small clad height and clad depth. The combination of 750 W laser power, 10 m/s scanning speed and 1 r/min feeding rare is selected as the desirable process parameters. The proposed optimization method is validated by both experiment design and theoretical calculation and can be extended to parameter selection for other types of metal powder. [ABSTRACT FROM AUTHOR]

This study was conducted to determine effects of dietary Fe levels on growth performance, hepatic lipid metabolism and antioxidant response for juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were fed six isonitrogenous and isolipidic diets containing Fe levels of 16.20, 34.80, 54.50, 76.44, 100.42 and 118.25 mg/kg for 8 weeks. Weight gain ( WG) and specific growth rate ( SGR) increased with dietary Fe levels from 16.20 to 54.50 mg/kg diet and then plateaued over the level. Feed conversion rate ( FCR) was highest and protein efficiency rate ( PER) was lowest for fish fed the lowest Fe levels of diet. Fe contents in whole body and liver increased with increasing dietary Fe levels. Hepatic lipid content was lowest, but mRNA levels of carnitine palmitoyltransferase ( CPT-1) and peroxisome proliferator-activated receptor α ( PPARα) were highest for fish fed 54.50 mg Fe/kg diet. Fish fed adequate dietary Fe levels reduced hepatic malondialdehyde ( MDA) level and increased activities of antioxidant enzymes Superoxide dismutase ( SOD), Catalase ( CAT) and GS. Based on the broken-line regression analysis of WG against dietary Fe levels, optimal dietary Fe requirement for yellow catfish was 55.73 mg Fe/kg diets. Fe-induced changes in MDA levels and antioxidant enzymatic activities paralleled with the change in hepatic lipid content, suggesting the potential relationship between oxidative stress and hepatic lipid accumulation in yellow catfish. [ABSTRACT FROM AUTHOR]

OBJECTIVE: RNA-seq data of colon adenocarcinoma (COAD) were analyzed with bioinformatics tools to discover critical genes in the disease. Relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. MATERIALS AND METHODS: RNA-seq data of COAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. False positive discovery (FDR) < 0.05 and |log2 (fold change)|> were set as the cut-offs to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress. GO enrichment analysis was performed for the DEGs in the gene coexpression network with DAVID. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed for the genes with KOBASS 2.0. Modules were identified with MCODE of Cytoscape. Relevant small molecules drugs were predicted by Connectivity map. Relevant miRNAs and TFs were searched by WebGestalt. RESULTS: A total of 457 DEGs, including 255 up-regulated and 202 down-regulated genes, were identified from 437 COAD and 39 control samples. A gene coexpression network was constructed containing 40 DEGs and 101 edges. The genes were mainly associated with collagen fibril organization, extracellular matrix organization and translation. Two modules were identified from the gene coexpression network, which were implicated in muscle contraction and extracellular matrix organization, respectively. Several critical genes were disclosed, such as MYH11, COL5A2 and ribosomal proteins. Nine relevant small molecule drugs were identified, such as scriptaid and STOCK1N-35874. Accordingly, a total of 17 TFs and 10 miRNAs related to COAD were acquired, such as ETS2, NFAT, AP4, miR-124A, MiR-9, miR-96 and let-7. CONCLUSIONS: Several critical genes and relevant drugs, TFs and miRNAs were revealed in COAD. These findings could advance the understanding of the disease and benefit therapy development. [ABSTRACT FROM AUTHOR]