Regulation of dndB Gene Expression in Streptomyces lividans

DNA sulfur modification is a unique modification occurring in the sugar-phosphate backbone of DNA, with a nonbridging oxygen atom substituted with sulfur in a sequence-specific and Rp stereo-specific manner. Bioinformatics, RNA-seq, and in vitro transcriptional analyses have shown that DNA sulfur modification may be involved in epigenetic regulation. However, the in vivo evidence supporting this assertion is not convincing. Here, we aimed to characterize two sulfur-modified sites near the dndB promoter region in Streptomyces lividans. Single mutation of either site had no effect on dndB transcription, whereas double mutation of both sites significantly elevated dndB expression. These findings suggested that DNA sulfur modification affected gene expression, and the role of DNA sulfur modification in epigenetic regulation depended on the number of sulfur-modified sites. We also identified an inverted repeat, the R repeat sequence, and showed that this sequence participated in the positive regulation of dndB gene expression

CircRNA-mediated regulation of brown adipose tissue adipogenesis

Adipose tissue represents a candidate target for the treatment of metabolic illnesses, such as obesity. Brown adipose tissue (BAT), an important heat source within the body, promotes metabolic health through fat consumption. Therefore, the induction of white fat browning may improve lipid metabolism. Currently, the specific roles of circRNA in BAT and white adipose tissue (WAT) remain elusive. Herein, we conducted circRNA expression profiling of mouse BAT and WAT using RNA-seq. We identified a total of 12,183 circRNAs, including 165 upregulated and 79 downregulated circRNAs between BAT and WAT. Differentially expressed (DE) circRNAs were associated with the mitochondrion, mitochondrial part, mitochondrial inner membrane, mitochondrial envelope, therefore, these circRNAs may affect the thermogenesis and lipid metabolism of BAT. Moreover, DE circRNAs were enriched in browning- and thermogenesis-related pathways, including AMPK and HIF-1 signaling. In addition, a novel circRNA, circOgdh, was found to be highly expressed in BAT, formed by back-splicing of the third and fourth exons of the Ogdh gene, and exhibited higher stability than linear Ogdh. circOgdh was mainly distributed in the cytoplasm and could sponge miR-34a-5p, upregulating the expression of Atgl, a key lipolysis gene, which enhanced brown adipocyte lipolysis and suppressed lipid droplet accumulation. Our findings offer in-depth knowledge of the modulatory functions of circRNAs in BAT adipogenesis

Developmental expression and function of DKKL1/Dkkl1 in humans and mice

Background: Experiments were designed to identify the developmental expression and function of the Dickkopf-Like1 (DKKL1/Dkkl1) gene in humans and mice. Methods: Mouse testes cDNA samples were collected at multiple postnatal times (days 4, 9, 18, 35, and 54, as well as at 6 months) and hybridized to Affymetrix mouse whole genome Genechips. To further characterize the homologous gene DKKL1 in human beings, the expression profiles between human adult testis and foetal testis were compared using Affymetrix human Genechips. The characteristics of DKKL1/Dkkl1 were analysed using various cellular and molecular biotechnologies. Results: The expression of Dkkl1 was not detected in mouse testes on days 4 or 9, but was present on days 18, 35, and 54, as well as at 6 months, which was confirmed by RT-PCR and Western blot results. Examination of the tissue distribution of Dkkl1 demonstrated that while Dkkl1 mRNA was abundantly expressed in testes, little to no expression of Dkkl1 was observed in the epididymis or other tissues. In an in vitro fertilization assay, a Dkkl1 antibody was found to significantly reduce fertilization. Human Genechips results showed that the hybridization signal intensity of DKKL1 was 405.56-fold higher in adult testis than in foetal testis. RT-PCR analysis of multiple human tissues indicated that DKKL1 mRNA was exclusively expressed in the testis. Western blot analysis also demonstrated that DKKL1 was mainly expressed in human testis with a molecular weight of approximately 34 kDa. Additionally, immunohistochemical staining showed that the DKKL1 protein was predominantly located in spermatocytes and round spermatids in human testes. An examination of the expression levels of DKKL1 in infertile male patients revealed that while no DKKL1 appeared in the testes of patients with Sertoli cell only syndrome (SCOS) or cryptorchidism, DKKL1 was observed with variable expression in patients with spermatogenic arrest. Conclusions: These results, together with previous studies, suggest that DKKL1/Dkkl1 may play an important role in testicular development and spermatogenesis and may be an important factor in male infertility.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000308911000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Endocrinology & MetabolismReproductive BiologySCI(E)3ARTICLEnull1

Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

Background: The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs. Methods: The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC. Results: The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients. Conclusion: To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC

Prognostic Values of Long Noncoding RNA <i>linc00152</i> in Various Carcinomas: An Updated Systematic Review and Meta-Analysis

Abstract Dysregulation of the long noncoding RNA linc00152 has been reported in various solid tumors. Here, we performed a synthetic analysis to clarify the clinical value of linc00152 as a prognostic indicator in malignant tumors. Article collection was conducted using several electronic databases, including PubMed, Web of Science, Medline, OVID, and Embase (up to February 13, 2018). The meta-analysis comprised nine original studies and 808 total patients. The application of a random-effects model revealed significant positive association between high expression level of linc00152 and lymph node metastasis (odds ratio [OR] = 2.93, 95% confidence interval [CI]: 1.88–4.57, p &amp;lt; .0001; I2 = 48.8, p = .119) and negative association with low-grade cancer (OR = 2.43, 95% CI: 1.51–3.92; I2 = 61.7, p = .033), while with tumor recurrence (hazard ratio [HR] = 3.32, 95% CI: 1.98–5.57, p &amp;lt; .0001; I2 = 0, p = .451) by fixed-effects model as the low heterogeneity. As demonstrated via the application of the fixed-effects model, Linc00152 overexpression is positively related to poor overall survival (pooled HR = 1.98, 95% CI: 1.70–2.31, p &amp;lt; .0001; I2 = 0%, p = .756) and poor disease-free survival (HR = 1.66, 95% CI: 1.20–2.29, p &amp;lt; .0001; I2 = 75.8%, p = .042) in human solid cancers. Statistically significant associations were additionally found with cancer type, sample size, and follow-up time. In conclusion, linc00152 is of potential value as a novel biomarker of lymph node metastasis and prognosis in human cancer. </jats:sec

Nonnegative singular value decomposition for microarray data analysis of spermatogenesis

Matrix factorization plays an important role in scientific computation. The widely used one is singular value decomposition (SVD) which approximates the original data matrix with three lower rank matrices with orthogonality constraints. Recently nonnegative matrix factorization (NMF) considering the nonnegativity of data makes the results more interpretable than those of SVD. However NMF finds only two factor matrices and there is no significant index as singular values of SVD which can be used for sorting learned basis vectors. In this paper we take into account the nonnegativity for SVD and propose nonnegative SVD (NNSVD). The preliminary results on the microarray data of spermatogenesis show that NNSVD has advantages of both SVD and NMF. ? 2008 IEEE.EI

Notice of Retraction: Spermatogenesis-Related Gene Selection by Singular Value Decomposition and Correlation Analysis

The aim of this study is to select significant genes associated with spermatogenesis. We use singular value decomposition to extract the principal component of the DNA microarray dataset and the expression profile of the first eigengene shows the expression tendency of most genes&apos; expression. Basing on this observation, we rank genes using correlation of each gene expression and the first eigengene&apos;s profile. Five kinds of correlation methods are considered and experimental results on a real spermatogenesis microarray dataset demonstrate that the cosine correlation method can find 75 informative genes among top 100 probes/genes. The selected significant genes, especially the top 10 probes/genes, are related to spermatogenesis through literature analysis. ? 2011 IEEE.EI