[Show abstract][Hide abstract] ABSTRACT: Scientific Reports 5 Article number: 14106; 10.1038/srep14106 published online: 16 September 2015 ; updated: 18 December 2015 . In this Article, there are typographical errors in the accession numbers: “The Whole Genome Shotgun project has been deposited in DDBJ/EMBL/GenBank as project accession PRJNA200657 and PRJNA200654 of donkey and Asiatic wild ass, respectively.
[Show abstract][Hide abstract] ABSTRACT: Epithelial ovarian cancer (EOC) is the most lethal and aggressive gynecological malignancy, and abnormal cellular metabolism significantly contributes to cancer onset and progression. Here, we report that miR-29b negatively regulates AKT2/AKT3 expression, causing HK2/PKM2 downregulation and leading to a decreased Warburg effect and slowed ovarian cancer progression. Compared to normal ovaries, ovaries with epithelial cancer exhibited lower miR-29b expression at both cellular/histological levels. Glucose consumption and lactate production experiments confirmed miR-29b's regulation of EOC metabolism. A luciferase reporter assay confirmed the direct binding of miR-29b to AKT2/AKT3 3' UTRs. miR-29b silencing correlated with increased expression of AKT2/3, pAKT2/3, HK2, and PKM2. Pyruvic acid and NAD+/NADH levels also changed when miR-29b expression was suppressed; this effect could be blocked by specific AKT inhibitors, suggesting the miR-29b-AKT axis regulates the Warburg effect in ovarian cancer. In xenograft mouse models, miR-29b inhibited tumor formation in vivo. In vivo imaging also demonstrated that miR-29b agomir inhibited the relative uptake of 18F-FDG in the xenograft tumors, suggesting that miR-29b over-expression could negatively modulate tumor glucose metabolism in vivo. Taken together, our study suggests that miR-29b regulates the Warburg effect in EOC via AKT2/AKT3 and may provide novel options for future treatments for EOC.
[Show abstract][Hide abstract] ABSTRACT: The donkey, like the horse, is a promising model for exploring karyotypic instability. We report the de novo whole-genome assemblies of the donkey and the Asiatic wild ass. Our results reflect the distinct characteristics of donkeys, including more effective energy metabolism and better immunity than horses. The donkey shows a steady demographic trajectory. We detected abundant satellite sequences in some inactive centromere regions but not in neocentromere regions, while ribosomal RNAs frequently emerged in neocentromere regions but not in the obsolete centromere regions. Expanded miRNA families and five newly discovered miRNA target genes involved in meiosis may be associated with fast karyotype evolution. APC/C, controlling sister chromatid segregation, cytokinesis, and the establishment of the G1 cell cycle phase were identified by analysis of miRNA targets and rapidly evolving genes.
[Show abstract][Hide abstract] ABSTRACT: Long non-coding RNAs (lncRNAs) have been recognized as a regulator of gene expression, and the deregulation of lncRNAs have been reported to be correlated with carcinogenesis and cancer progression. To explore the function of lncRNA in endometrial carcinoma, we analyzed the expression profiles of lncRNAs and coding genes in 3 paired endometrial carcinoma and adjacent non-tumor tissues, using a microarray. The results of microarray analysis indicated a significant difference in lncRNA and coding gene expression between endometrial carcinoma and their paired adjacent non-tumor tissues. A total of 53 lncRNAs (fold change >2.0, p-value <0.05) were found to be differently expressed in endometrial carcinoma compared to the normal controls. Among these ASLNC04080 was the most significantly upregulated lncRNA in microarray data, highly expressed in 22 out of 24 endometrial carcinoma tissues and HEC-1-B cell line. ASLNC04080 is 1867nt in length, consist of 6 exons, and locates at 1 p35.3(chr1: -28905061 - -28909492). In addition, 46 coding gene transcripts were differentially expressed (fold change >2.0, p-value <0.05) between endometrial carcinoma and adjacent non-tumor tissues. Pathway and gene ontology analysis demonstrated that these deregulated transcripts were involved in multiple signal pathways, biological processes, cellular components and molecular functions. Moreover, the ASLNC04080 lncRNA expression was correlated with 19 coding genes, and may contribute to endometrial carcinoma genesis and progression by co-regulating with coding gene. Expression inhibition of lncRNA ASLNC04080 in HEC-1-B cells caused repression of cell proliferation, increased cell apoptosis, and G1 phase arrest. These results suggested a potential function of ASLNC04080 in endometrial carcinoma genesis and progression.
No preview · Article · Feb 2015 · International Journal of Oncology
[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) are essential to the understanding of population genetic variation and diversity. Here, we performed restriction-site-associated DNA sequencing (RAD-seq) on 72 individuals from 13 Chinese indigenous and three introduced chicken breeds. A total of 620 million reads were obtained using an Illumina Hiseq2000 sequencer. An average of 75 587 SNPs were identified from each individual. Further filtering strictly validated 28 895 SNPs candidates for all populations. When compared with the NCBI dbSNP (chicken_9031), 15 404 SNPs were new discoveries. In this study, RAD-seq was performed for the first time on chickens, implicating the remarkable effectiveness and potential applications on genetic analysis and breeding technique for whole-genome selection in chicken and other agricultural animals.
[Show abstract][Hide abstract] ABSTRACT: The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT) is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S)-Rg3, which reduces the expression of hypoxia-inducible factor 1α (HIF-1α) by activating the ubiquitin-proteasome pathway to promote HIF-1α degradation. A decrease in HIF-1α in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S)-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy.
[Show abstract][Hide abstract] ABSTRACT: Karyotypic diversification is more prominent in Equus species than in other mammals. Here, using next generation sequencing technology, we generated and de novo assembled quality genomes sequences for a male wild horse (Przewalski's horse) and a male domestic horse (Mongolian horse), with about 93-fold and 91-fold coverage, respectively. Portion of Y chromosome from wild horse assemblies (3 M bp) and Mongolian horse (2 M bp) were also sequenced and de novo assembled. We confirmed a Robertsonian translocation event through the wild horse's chromosomes 23 and 24, which contained sequences that were highly homologous with those on the domestic horse's chromosome 5. The four main types of rearrangement, insertion of unknown origin, inserted duplication, inversion, and relocation, are not evenly distributed on all the chromosomes, and some chromosomes, such as the X chromosome, contain more rearrangements than others, and the number of inversions is far less than the number of insertions and relocations in the horse genome. Furthermore, we discovered the percentages of LINE_L1 and LTR_ERV1 are significantly increased in rearrangement regions. The analysis results of the two representative Equus species genomes improved our knowledge of Equus chromosome rearrangement and karyotype evolution.
[Show abstract][Hide abstract] ABSTRACT: The abundance of gut microbiota can be viewed as a quantitative trait, which is affected by the genetics and environment of the host. To quantify the effects of host genetics, we calculated the heritability of abundance of specific microorganisms and genetic correlations among them in the gut microbiota of two lines of chickens maintained under the same husbandry and dietary regimes. The lines, which originated from a common founder population, had undergone >50 generations of selection for high (HW) or low (LW) 56-day body weight and now differ by more than 10-fold in body weight at selection age. We identified families of Paenibacillaceae, Streptococcaceae, Helicobacteraceae, and Burkholderiaceae that had moderate heritabilities. Although there were no obvious phenotypic correlations among gut microbiota, significant genetic correlations were observed. Moreover, the effects were modified by genetic selection for body weight, which altered the quantitative genetic background of the host. Heritabilities for Bacillaceae, Flavobacteriaceae, Helicobacteraceae, Comamonadaceae, Enterococcaceae, and Streptococcaceae were moderate in LW line and little to zero in the HW line. These results suggest that loci associated with these microbiota families, while exhibiting genetic variation in LW, have been fixed in HW line. Also, long term selection for body weight has altered the genetic correlations among gut microbiota. No microbiota families had significant heritabilities in both the LW and HW lines suggesting that the presence and/or absence of a particular microbiota family either has a strong growth promoting or inhibiting effect, but not both. These results demonstrate that the quantitative genetics of the host have considerable influence on the gut microbiota.
[Show abstract][Hide abstract] ABSTRACT: Regulator of G-protein Signaling 10 (Rgs10) plays an important function in osteoclast differentiation. However, the role of Rgs10 in immune cells and inflammatory responses, which activate osteoclasts in inflammatory lesions, such as bacteria-induced periodontal disease lesions, remains largely unknown. In this study, we used an adeno-associated virus (AAV-) mediated RNAi (AAV-shRNA-Rgs10) knockdown approach to study Rgs10's function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease. We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption, in vitro and in vivo. Interestingly, local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells, T-cells and osteoclasts, and protected the periodontal tissues from local inflammatory damage and bone destruction. Importantly, AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgs10 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and activation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is one of the most serious under-diagnosed and under-treated recessive diseases, leading to increased mortality and morbidity as well as huge economic burden. The fundamental reason for the occurrence of osteoporosis lies in the disequilibrium between bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. Osteoclast-osteoblast communication plays important roles in the maintenance of hemeostasis. In this review, we present the detailed mechanisms of this communication, including modes of diffusible paracrine factors, cell-cell direct contact and cell-bone matrix interaction. We demonstrate that osteoclasts (or osteoblasts) could not only secrete cytokines, growth factors, chemokines and function in a paracrine manner, but also express molecules on their membranes to bind to the receptors on osteoblasts (or osteoclasts) to transduce bidirectional signals. Moreover, growth factors and cytokines deliberated from bone matrix during bone resorption could also regulate the function of both osteoblasts and osteoclasts. This review gives the latest knowledge of communication factors, some of which are emerging as novel therapeutic targets for future development of antiosteoporotic drugs.
No preview · Article · Aug 2013 · Current drug targets
[Show abstract][Hide abstract] ABSTRACT: Host genotype and gender are among the factors that influence the composition of gut microbiota. We studied the population structure of gut microbiota in two lines of chickens maintained under the same husbandry and dietary regimes. The lines, which originated from a common founder population, had undergone 54 generations of selection for high (HW) or low (LW) 56-day body weight, and now differ by more than 10-fold in body weight at selection age. Of 190 microbiome species, 68 were affected by genotype (line), gender, and genotype by gender interactions. Fifteen of the 68 species belong to Lactobacillus. Species affected by genotype, gender, and the genotype by gender interaction, were 29, 48, and 12, respectively. Species affected by gender were 30 and 17 in the HW and LW lines, respectively. Thus, under a common diet and husbandry host quantitative genotype and gender influenced gut microbiota composite.
Full-text · Article · Jan 2013 · Scientific Reports
[Show abstract][Hide abstract] ABSTRACT: Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 × 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system.
Full-text · Article · Nov 2012 · Nature Communications
[Show abstract][Hide abstract] ABSTRACT: Objectives Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH) are highly prevalent in the aging male population and cause substantial adverse effects on health. There are strong evidences from multiple epidemological studies that LUTS and hypertension are correlated. BPH/LUTS and hypertension are often coexist in the older men. Men with bothersome LUTS may predispose patients to present with various conditions including hypertension, depression and so on. Severe LUTS are likely to constitute a risk factor for the development of hypertension. α(1)-blockers initially introduced for the management of hypertension and have become first-line medical therapy options for BPH/LUTS. This study was conducted to describe the efficacy of the daily therapy, doxazosin as an α(1)-blocker, on BPH/LUTS in men with mild hypertension.
Objectives To evaluate the safety and the therapeutic efficacy of doxazosin for mild hypertesion patients with BPH/LUTS.
Methods A total of 52 mild hypertension patients concomitant with BPH/LUTS (International Prostate Symptom Score-IPSS>7) at the first visit in our clinic were enrolled in this trial. They were assessed based on IPSS and IPSS-Quality of Life for BPH/LUTS and measurement of blood pressure (BP) in the patients with mild hypertension after excluding those with normotensive and moderate-to-severe hypertension. They were treated with 4 mg of doxazosin once daily for 12 weeks. IPSS, IPSS quality of life, BPH Impact Index and BP measurement were evaluated every 4 weeks. Safety was mainly assessed via spontaneous reports of adverse events.
Results After 12 weeks of the medication, changes in IPSS in mild hypertension men concomitant with BPH/LUTS were significantly different before and after treatment (12.6±3.8 vs 8.1±2.6, p<0.01). Doxazosin demonstrated efficacy in lowering the score for IPSS and relieving LUTS. Of them, systolic and diastolic blood pressure of 39 patients (75.0%) decreased to normal. Doxazosin was generally well tolerated. No orthostatic hypotension and other blood pressure-related adverse profiles occurred in all patients.
Conclusions Doxazosin therapy appears to be efficacious in both relieving LUTS and decreasing blood pressure in mild hypertension men concomitant with BPH/LUTS.
No preview · Article · Oct 2012 · Heart (British Cardiac Society)