Publications by authors named "Shiqiang Zhang"

66 Publications

Applying the Super-EBM model and spatial Durbin model to examining total-factor ecological efficiency from a multi-dimensional perspective: evidence from China.

Environ Sci Pollut Res Int 2021 Aug 7. Epub 2021 Aug 7.

School of Public Economics and Administration, Shanghai University of Finance and Economics, Shanghai, 200433, China.

Ecological efficiency mainly emphasizes the importance of balancing the relationships between natural resources, energy, the ecological environment and economic growth, which has aroused widespread concern worldwide. China's rapid economic development has inevitably been accompanied by serious resource exhaustion, environmental pollution and ecological deterioration in the past several decades, which has brought huge challenges to China's sustainable development. Therefore, establishing the evaluation framework of total-factor ecological efficiency (TFEE) and identifying its driving force have a great significance for improving China's sustainable development capabilities. First, an ecological efficiency evaluation framework is established based on the theory of total-factor analysis. Second, the super efficient hybrid distance model considers undesirable output and measures TFEE nationwide in 30 provinces and four regions during the period 2003-2017. Finally, the spatial effect of TFEE and its influencing factors are examined by using a spatial Durbin model. The empirical results show that (1) nationwide and regional TFEEs have different degrees of decline during the study period. There were significant differences among the 30 provinces and four regions. Beijing, Tianjin and Shanghai are efficient, while the other provinces have not been as effective. The TFEEs of the four regions are not effective with an ordering of eastern > northeast > central > western. (2) Moran's I index shows that the TFEE nationwide has a positive spatial autocorrelation with strong spatial agglomeration. However, the spatial distribution pattern of TFEE in China was unstable and labile. The Moran scatter plot indicates that China's provincial TFEE has not only spatial dependence characteristics but also differences in spatial correlation. (3) Most factors are bound up with TFEE to various degrees: technological progress (TP), industrial agglomeration (IG) and human capital (HC) play a positive role, while industrial structure (IS), the level of urbanization (CITY) and energy intensity (EI) play a negative role. Additionally, environmental regulation (GZ) shows a U-type relationship with TFEE. The level of economic development (GDP) and foreign direct investment (FDI) cannot have a significant impact on TFEE at this stage. (4) The spatial Durbin model results show that TFEE has a significant spatial spillover effect, and the improvement of the TFEE of a province will increase the TFEE of neighbouring provinces. The confirmed spatial spillover effects of technological progress (TP), industrial structure (IS), the level of urbanization (CITY), industrial agglomeration (IG) and human capital (HC) can significantly impact the TFEE of neighbouring provinces. Among them, technological progress (TP), the level of urbanization (CITY) and human capital (HC) can significantly improve the TFEE of neighbouring provinces, and the level of economic development (GDP) and foreign direct investment (FDI) can significantly inhibit the improvement of TFEE in neighbouring provinces.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-15770-wDOI Listing
August 2021

A calcium phosphate drug carrier loading with 5-fluorouracil achieving a synergistic effect for pancreatic cancer therapy.

J Colloid Interface Sci 2021 Jul 20;605:263-273. Epub 2021 Jul 20.

The Seventh Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China. Electronic address:

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH particles could be efficiently uptaken by cancer cells, and then decompose into Ca and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH drug delivery platform for enhanced 5Fu chemotherapeutic effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.07.080DOI Listing
July 2021

Evaluation of immune status in testis and macrophage polarization associated with testicular damage in patients with nonobstructive azoospermia.

Am J Reprod Immunol 2021 Jun 30:e13481. Epub 2021 Jun 30.

Department of Urology, Fujian Medical University Union Hospital, Fuzhou, China.

Objective: Immune cells residing in the testicular interstitial space form the immunological microenvironment of the testis. They are assumed to play a role in maintaining testicular homeostasis and immune privilege. However, the immune status and related cell polarization in patients with nonobstructive azoospermia (NOA) remains poorly characterized. System evaluation of the testis immunological microenvironment in NOA patients may help to reveal the mechanisms of idiopathic azoospermia.

Study Design: The gene expression patterns of immune cells in normal human testes were systematically analyzed by single-cell RNA sequencing (scRNA-seq) and preliminarily verification by the human protein atlas (HPA) online database. The immune cell infiltration profiles and immune status of patients with NOA was analyzed by single-sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) based on four independent public microarray datasets (GSE45885, GSE45887, GSE9210, and GSE145467), obtained from Gene Expression Omnibus (GEO) online database. The relationship between immune cells and spermatogenesis score was further analyzed by Spearman correlation analysis. Finally, immunohistochemistry (IHC) staining was performed to identify the main immune cell types and their polarization status in patients with NOA.

Results: Both scRNA-seq and HPA analysis showed that testicular macrophages represent the largest pool of immune cells in the normal testis, and also exhibit an attenuated inflammatory response by expressing high levels of tolerance proteins (CD163, IL-10, TGF-β, and VEGF) and reduced expression of TLR signaling pathway-related genes. Correlation analysis revealed that the testicular immune score and macrophages including M1 and M2 macrophages were significantly negatively correlated with spermatogenesis score in patients with NOA (GSE45885 and GSE45887). In addition, the number of M1 and M2 macrophages was significantly higher in patients with NOA (GSE9210 and GSE145467) than in normal testis. GSVA analysis indicated that the immunological microenvironment in NOA tissues was manifested by activated immune system and pro-inflammatory status. IHC staining results showed that the number of M1 and M2 macrophages was significantly higher in NOA tissues than in normal testis and negatively correlated with the Johnson score.

Conclusion: Testicular macrophage polarization may play a vital role in NOA development and is a promising potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13481DOI Listing
June 2021

Study on optimization and evaluation system of traditional Chinese medicine rehabilitation program for swallowing disorder after stroke.

Medicine (Baltimore) 2021 May;100(19):e25731

Rehabilitation Center.

Background: Acupuncture has a long history in China and is currently widely used in clinical practice. However, there is no large sample data confirming the effectiveness of acupuncture in treating stroke and its sequelae. This article presents a study protocol for a multicenter, randomized, controlled trial for evaluating the efficacy of acupuncture in treating post-stroke dysphagia.

Methods/design: A randomized controlled trial will be conducted in three hospitals in Heilongjiang, Changchun, and Beijing. A total of 252 patients with post-stroke swallowing ability will be randomly divided into two groups; specifically, the experimental group, which will receive acupuncture treatment, and the control group, which will undergo rehabilitation training for 2 weeks. The main results will be evaluated using the standard swallowing function scale, videofluoroscopic swallowing examination, and functional magnetic resonance imaging. The secondary observation indexes will include surface electromyography signal analysis and the modified Barthel index. Measurements will be obtained before treatment, as well as 1 week, 2 weeks, and 1 month after treatment.

Discussion: This trial could clarify the effectiveness of acupuncture in stroke; moreover, it will determine whether acupuncture can improve swallowing function.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000030994.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133205PMC
May 2021

Solution combustion synthesis of a nanometer-scale CoO anode material for Li-ion batteries.

Beilstein J Nanotechnol 2021 10;12:424-431. Epub 2021 May 10.

Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106 Warsaw, Poland.

A novel solution combustion synthesis of nanoscale spinel-structured CoO powder was proposed in this work. The obtained material was composed of loosely arranged nanoparticles whose average diameter was about 36 nm. The as-prepared cobalt oxide powder was also tested as the anode material for Li-ion batteries and revealed specific capacities of 1060 and 533 mAh·g after 100 cycles at charge-discharge current densities of 100 and 500 mA·g, respectively. Moreover, electrochemical measurements indicate that even though the synthesized nanomaterial possesses a low active surface area, it exhibits a relatively high specific capacity measured at 100 mA·g after 100 cycles and a quite good rate capability at current densities between 50 and 5000 mA·g.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3762/bjnano.12.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144916PMC
May 2021

Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to define a pluripotency gene regulatory network.

FASEB J 2021 06;35(6):e21664

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China.

The pluripotency gene regulatory network of porcine induced pluripotent stem cells(piPSCs), especially in epigenetics, remains elusive. To determine the biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202100230RDOI Listing
June 2021

Systematic Chromatin Accessibility Analysis Based on Different Immunological Subtypes of Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 16;11:575425. Epub 2021 Apr 16.

Department of Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Background: Recent research of clear cell renal cell carcinoma (ccRCC) is focused on the tumor immune microenvironment (TIME). Chromatin accessibility is critical for regulation of gene expression. However, its role in different immunological subtypes of ccRCC based on immune cell infiltration has not been systematically studied.

Methods: Five hundred thirty patient data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) were adopted to estimate immune cell infiltration. Twenty-four types of immune cells were evaluated with single-sample Gene Set Enrichment Analysis (ssGSEA). Patients were divided into two clusters based on immune cell infiltration. Systematic chromatin accessibility analysis was conducted based on the two clusters.

Results: We compared the relative expression of the immune gene signatures among 530 patients of TCGA-KIRC using ssGSEA. Overall survival (OS) analysis revealed 10 types of immune cells were significantly associated with prognosis. Patients were divided into two clusters based on 24 types of immune cell infiltration. Immune cell signals as well as PD-1/PD-L1 signal were higher in cluster 1. Among the two clusters, 2,400 differential peaks were found in TCGA-KIRC Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) data. The distribution of differential peaks and prognosis-related immune cells in 23 chromosomes are essentially the same. There is no peak distribution downstream. The proportion of peaks upstream of the 5' transcription start site decreases, and both sides of binding regions of the TSS 0.1-1 kb becomes smaller. Enrichment analysis of GO and KEGG of these differential peaks showed that they are remarkably related to the immune regulation in tumor microenvironment. Known motifs and motifs were found by linking motif annotations to different peaks. Survival analysis of related motif transcription factors were prognostic. The GSEA enrichment analysis showed that high SP1 expression positively correlates with TGF-beta signaling and inflammatory response, while negatively correlates with TNF-alpha signaling NFKB. High KLF12 expression negatively correlates with interferon gamma response, IL2-STAT5 signaling, TNF-alpha signaling NFKB, IL6-JAK-STAT3 signaling.

Conclusion: The abnormality of chromatin accessibility may play an important regulatory role in ccRCC immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.575425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085385PMC
April 2021

Pregnancy Promotes the Recurrence of Cerebellar Hemangioblastoma?

J Craniofac Surg 2021 Apr 15. Epub 2021 Apr 15.

Department of Neurosurgery of Wuhan Third Hospital Department of Surgery and Anesthesia, Taikang Tongji (Wuhan) Hospital, Wuhan Department of Neurosurgery of Shenzhen People's Hospital, Shenzhen, China.

Abstract: Cerebellar hemangioblastomas with pregnancy is rare, but coexistence of pregnancy and recurrent cerebellar hemangioblastomas is rather rare. And coexistence of other diseases during pregnancy usually leads to misdiagnosis because of pregnancy reaction. A 29-year-old woman, at the 8th week of pregnancy, complained of nausea, vomiting, and episodic posterior occipital pain and was misdiagnosed pregnancy reaction without any special treatment during her several visits to local hospital. The patient was diagnosed cerebellar hemangioblastomas 14 years ago, after surgery, she received regular re-examination without recurrence. At the 15th week of pregnancy, the situation of the patient got worse, and she was admitted to our hospital. Brain magnetic resonance imaging showed a lesion in cerebellum. It was considered to be cerebellar hemangioblastomas and was confirmed finally by postoperative pathological examination. In clinical practice, differential diagnosis is of great importance during pregnancy because many other diseases can mimic pregnancy reaction. In this patient, the intracranial hypertension caused by recurrent cerebellar hemangioblastomas was misdiagnosed as pregnancy reaction and it was suggested that the change of hormones, neuroendocrine, and cardiovascular function promoted the recurrence of cerebellar hemangioblastomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000007683DOI Listing
April 2021

Herbal formula of Bushen Jianpi combined with sorafenib inhibits hepatocellular carcinoma growth by promoting cell apoptosis and blocking the cell cycle.

J Tradit Chin Med 2021 04;41(2):194-202

Oncology Department, Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China.

Objective: To investigate the efficacy of an herbal formula of Bushen Jianpi ( BSJP) combined with sorafenib on hepatocellular carcinoma (HCC) in vitro and in vivo, and to study the underlying mechanisms of action.

Methods: BSJP, a mixture of 12 raw herbs, was extracted in 70% alcohol/30% water and freeze-dried into a powder. The in vitro effects of BSJP alone, sorafenib alone, and their combination on cell survival, apoptosis, and cell cycle distribution were evaluated in HCC cell lines HCCLM3, HepG2, and SMMC-7721. The expression of B-cell lymphoma-2 (Bcl-2), caspase-3, and caspase-9 in HCCLM3 cells was measured using Western blots after drug administration. The in vivo effects of BSJP and sorafenib were evaluated in a tumor surgical resection model using 4-week old male athymic BALB/c nude mice injected with HCCLM3 cells. Immunohistochemical analysis of tumor tissues was performed to evaluate the effects of BSJP alone, sorafenib alone, and their combination on the expression of caspase-3, caspase-9, and Bcl-2.

Results: BSJP decreased the survival rate of HCC cell lines, and the combination of BSJP and sorafenib further decreased the survival rate. BSJP significantly promoted cell apoptosis and blocked cell-cycle progression in HCCLM3, HepG2, and SMMC-7721 cells in a dose-dependent manner. Furthermore, the administration of BSJP and sorafenib inhibited the growth of HCCLM3 cell xenografts in nude mice, with no reduction in body weight. In vivo and in vitro experiments showed that BSJP combined with sorafenib could significantly decrease the expression of Bcl-2.

Conclusion: Our findings suggest that the herbal formula of BSJP is a potential HCC antitumor agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2021

Epigenetic Age Acceleration of Stomach Adenocarcinoma Associated With Tumor Stemness Features, Immunoactivation, and Favorable Prognosis.

Front Genet 2021 18;12:563051. Epub 2021 Mar 18.

Center of Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Abnormal DNA methylation (DNAm) age has been assumed to be an indicator for canceration and all-cause mortality. However, associations between DNAm age and molecular features of stomach adenocarcinoma (STAD), and its prognosis have not been systematically studied. We calculated the DNAm age of 591 STAD samples and 115 normal stomach samples from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) database using the Horvath's clock model. Meanwhile, we utilized survival analysis to evaluate the prognostic value of DNAm age and epigenetic age acceleration shift. In addition, we performed weighted gene co-expression network analysis (WGCNA) to identify DNAm age-associated gene modules and pathways. Finally, the association between DNAm age and molecular features was performed by correlation analysis. DNA methylation age was significantly correlated with chronological age in normal gastric tissues ( = 0.85, < 0.0001), but it was not associated with chronological age in STAD samples ( = 0.060, = 0.2369). Compared with tumor adjacent normal tissue, the DNAm age of STAD tissues was significantly decreased. Meanwhile, chronological age in STAD samples was higher than its DNAm age. Both DNAm age and epigenetic acceleration shift were associated with the prognosis of STAD patients. By using correlation analysis, we also found that DNAm age was associated with immunoactivation and stemness in STAD samples. In summary, epigenetic age acceleration of STAD was associated with tumor stemness, immunoactivation, and favorable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.563051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012546PMC
March 2021

Reactive oxygen species and glutathione dual responsive nanoparticles for enhanced prostate cancer therapy.

Mater Sci Eng C Mater Biol Appl 2021 Apr 11;123:111956. Epub 2021 Feb 11.

Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address:

Docetaxel (DTX)-based chemotherapy of prostate cancer is still confronted with significant challenges due to insufficient drug accumulation at the tumor sites and the systemic side effects on normal cells and organs. Tumor microenvironment-responsive nanosized drug delivery systems have shown enormous potential to improve the anticancer efficacy and minimize the systemic side effects of chemotherapeutics. However, most of the currently redox-responsive nanoparticles respond only to single stimuli, which compromise the treatment effect. Hence, inspired by the abundance of reactive oxygen species (ROS) and intracellular glutathione (GSH) in cancer cells, we proposed a unique ROS and GSH dual responsive nanocarrier (PCL-SS) for DTX delivery. The DTX-loaded PCL-SS nanoparticles ([email protected] NPs) were not only stable in a normal physiological environment but also rapidly triggered DTX release in prostate cancer cells. In vitro experiments showed that [email protected] NPs had robust prostate cancer cell cytotoxicity, induced cell apoptosis, inhibited cell migration and invasion and exhibited satisfactory biocompatibility. In mice bearing orthotopic prostate cancer, [email protected] NPs could accumulate in orthotopic tumor sites and then significantly weaken tumor growth by inhibiting prostate cancer cell proliferation and inducing cell apoptosis, without obvious damages to major organs. Overall, this dual responsive nanosized drug delivery system may act as a promising therapeutic option for prostate cancer chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.111956DOI Listing
April 2021

YAF2 exerts anti-apoptotic effect in human tumor cells in a FANK1- and phosphorylation-dependent manner.

Biochem Biophys Res Commun 2021 05 27;554:99-106. Epub 2021 Mar 27.

Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. Electronic address:

YY1-associated factor 2 (YAF2) was frequently reported to modulate target gene transcription through both epigenetic and non-epigenetic means. However, other mechanisms were also utilized by YAF2 to carry out its biological functions. Here, we demonstrated that YAF2 from human tumor and non-tumor cells were mainly expressed as Serine 167 phosphorylated form. Further studies showed that the phosphorylated YAF2 up-regulated while its knockdown by specific siRNAs reduced fibronectin type III and ankyrin repeat domains 1 (FANK1) protein level. Mechanistic exploration disclosed that phosphorylated YAF2 inhibit proteasomal degradation of polyubiquitinated FANK1, leading to its increased stability. We then validated their interaction, and displayed that the FN3 domain of FANK1 binds to amino-terminal of YAF2. Functional studies showed that phosphorylated YAF2 inhibits tumor cell apoptosis in a FANK1-dependent manner. Taken together, our current findings demonstrated that phosphorylated YAF2 exhibits anti-apoptotic activity through targeting FANK1 expression in human tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.03.105DOI Listing
May 2021

Multi-omics analysis of tumor angiogenesis characteristics and potential epigenetic regulation mechanisms in renal clear cell carcinoma.

Cell Commun Signal 2021 Mar 24;19(1):39. Epub 2021 Mar 24.

Department of Urology, Fujian Province, Fujian Medical University Union Hospital, Gulou District, 29 Xinquan Road, Fuzhou, 200001, People's Republic of China.

Background: Tumor angiogenesis, an essential process for cancer proliferation and metastasis, has a critical role in prognostic of kidney renal clear cell carcinoma (KIRC), as well as a target in guiding treatment with antiangiogenic agents. However, tumor angiogenesis subtypes and potential epigenetic regulation mechanisms in KIRC patient remains poorly characterized. System evaluation of angiogenesis subtypes in KIRC patient might help to reveal the mechanisms of KIRC and develop more target treatments for patients.

Method: Ten independent tumor angiogenesis signatures were obtained from molecular signatures database (MSigDB) and gene set variation analysis was performed to calculate the angiogenesis score in silico using the Cancer Genome Atlas (TCGA) KIRC dataset. Tumor angiogenesis subtypes in 539 TCGA-KIRC patients were identified using consensus clustering analysis. The potential regulation mechanisms was studied using gene mutation, copy number variation, and differential methylation analysis (DMA). The master transcription factors (MTF) that cause the difference in tumor angiogenesis signals were completed by transcription factor enrichment analysis.

Results: The angiogenesis score of a prognosis related angiogenesis signature including 189 genes was significantly correlated with immune score, stroma score, hypoxia score, and vascular endothelial growth factor (VEGF) signal score in 539 TCGA KIRC patients. MMRN2, CLEC14A, ACVRL1, EFNB2, and TEK in candidate gene set showed highest correlation coefficient with angiogenesis score in TCGA-KIRC patients. In addition, all of them were associated with overall survival in both TCGA-KIRC and E-MTAB-1980 KIRC data. Clustering analysis based on 183 genes in angiogenesis signature identified two prognosis related angiogenesis subtypes in TCGA KIRC patients. Two clusters also showed different angiogenesis score, immune score, stroma score, hypoxia score, VEGF signal score, and microenvironment score. DMA identified 59,654 differential methylation sites between two clusters and part of these sites were correlated with tumor angiogenesis genes including CDH13, COL4A3, and RHOB. In addition, RFX2, SOX13, and THRA were identified as top three MTF in regulating angiogenesis signature in KIRC patients.

Conclusion: Our study indicate that evaluation the angiogenesis subtypes of KIRC based on angiogenesis signature with 183 genes and potential epigenetic mechanisms may help to develop more target treatments for KIRC patients. Video Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12964-021-00728-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992844PMC
March 2021

Case Report: Dendritic Cells and Macrophages Capture Sperm in Chronically Inflamed Human Epididymis.

Front Immunol 2021 23;12:629680. Epub 2021 Feb 23.

Department of Urology, Fujian Medical University Union Hospital, Fuzhou, China.

Chronic inflammation of the male genital tract is thought to be a primary etiological factor of male infertility. The abundance and activation of macrophages and dendritic cells in patients with chronic inflammation of genital tract were closely associated with oligozoospermia and asthenospermia. Chronic epididymitis appears to be more important than seminal vesiculitis or prostatitis due to the direct interaction between spermatozoa and epididymal inflammatory cells. In this study, we present a case report of a 41-year-old male with oligoasthenospermia and chronic epididymitis. Hematoxylin-eosin staining and immunofluorescence analyses showed that antigen presenting cells including macrophages and dendritic cells were found capturing spermatozoa in the lumen of cauda epididymis. To our knowledge, this is the first case report that directly observed dendritic cells capturing spermatozoa in the lumen of an inflamed epididymis. This finding directly explains chronic epididymitis as the possible cause of oligospermia in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.629680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942197PMC
September 2021

Promotes the Proliferation of Spermatogonial Stem Cells by Activating ERK Signaling.

Stem Cells Int 2021 29;2021:6668658. Epub 2021 Jan 29.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.

The future fertility of males with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Spermatogonial stem cell transplantation is believed to be a way to restore fertility in men. However, the survival efficiency of transplanted cells is still low. Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked () located on the Y chromosome of male animals is a coding gene of eIF2 which mainly functions in translation initiation. Recently, the emerging role of in spermatogenesis has been emphasized in several studies. However, the underlying mechanism is still unclear. In addition, how functions in large animals remains largely unknown. In this study, we obtained the CDS sequence of the gene from the testis of dairy goats and found that this gene was highly expressed in the testis and was evolutionarily conserved among different species. Interestingly, overexpression of promoted the proliferation of spermatogonial stem cells of dairy goats by activating the ERK signaling pathway. In animal experiments, overexpressing promoted transplanted goat spermatogonial stem cells and produced more colonies after microinjection into the seminiferous tubules of infertile mice. In conclusion, our study highlights an undiscovered role of in dairy goat reproduction. This finding may provide an important basis for future works regarding male spermatogenic cell restoration and represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6668658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869416PMC
January 2021

The Bayesian Inference of Pareto Models Based on Information Geometry.

Entropy (Basel) 2020 Dec 30;23(1). Epub 2020 Dec 30.

School of Mathematics and Statistics, Beijing Institute of Technology, Beijing 100081, China.

Bayesian methods have been rapidly developed due to the important role of explicable causality in practical problems. We develope geometric approaches to Bayesian inference of Pareto models, and give an application to the analysis of sea clutter. For Pareto two-parameter model, we show the non-existence of α-parallel prior in general, hence we adopt Jeffreys prior to deal with the Bayesian inference. Considering geodesic distance as the loss function, an estimation in the sense of minimal mean geodesic distance is obtained. Meanwhile, by involving Al-Bayyati's loss function we gain a new class of Bayesian estimations. In the simulation, for sea clutter, we adopt Pareto model to acquire various types of parameter estimations and the posterior prediction results. Simulation results show the advantages of the Bayesian estimations proposed and the posterior prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e23010045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823987PMC
December 2020

Rigid Shape Registration Based on Extended Hamiltonian Learning.

Entropy (Basel) 2020 May 12;22(5). Epub 2020 May 12.

School of Mathematics and Statistics, Beijing Institute of Technology, Beijing 100081, China.

Shape registration, finding the correct alignment of two sets of data, plays a significant role in computer vision such as objection recognition and image analysis. The iterative closest point (ICP) algorithm is one of well known and widely used algorithms in this area. The main purpose of this paper is to incorporate ICP with the fast convergent extended Hamiltonian learning (EHL), so called , to perform planar and spatial rigid shape registration. By treating the registration error as the potential for the extended Hamiltonian system, the rigid shape registration is modelled as an optimization problem on the special Euclidean group S E ( n ) ( n = 2 , 3 ) . Our method is robust to initial values and parameters. Compared with some state-of-art methods, our approach shows better efficiency and accuracy by simulation experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e22050539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517035PMC
May 2020

Etv5 safeguards trophoblast stem cells differentiation from mouse EPSCs by regulating fibroblast growth factor receptor 2.

Mol Biol Rep 2020 Dec 6;47(12):9259-9269. Epub 2020 Nov 6.

College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, 712100, Yangling, China.

Previous studies have demonstrated that transcription factor Etv5 plays an important role in the segregation between epiblast and primitive endoderm at the second fate decision of early embryo. However, it remains elusive whether Etv5 functions in the segregation between inner cell mass and trophectoderm at the first cell fate decision. In this study, we firstly generated Etv5 knockout mouse embryonic stem cells (mESCs) by CRISPR/Cas9, then converted them into extended potential stem cells (EPSCs) by culturing the cells in small molecule cocktail medium LCDM (LIF, CHIR99021, (S)-(+)-dimethindene maleate, minocycline hydrochloride), and finally investigated their differentiation efficiency of trophoblast stem cells (TSCs). The results showed that Etv5 knockout significantly decreased the efficiency of TSCs (CDX2) differentiated from EPSCs. In addition, Etv5 knockout resulted in higher incidence of the differentiated cells with tetraploid and octoploid than that from wild type. Mechanistically, Etv5 was activated by extracellular-signal-regulated kinase (ERK) signaling pathway; in turn, Etv5 had a positive feedback on the expression of fibroblast growth factor receptor 2 (FGFR2) which lies upstream of ERK. Etv5 knockout decreased the expression of FGFR2, whose binding with fibroblast growth factor 4 was essentially needed for TSCs differentiation. Collectively, the findings in this study suggest that Etv5 is required to safeguard the TSCs differentiation by regulating FGFR2 and provide new clues to understand the specification of trophectoderm in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-020-05969-4DOI Listing
December 2020

Combustion characteristics and typical pollutant emissions of corn stalk blending with municipal sewage sludge.

Environ Sci Pollut Res Int 2021 Feb 6;28(8):9792-9805. Epub 2020 Nov 6.

Engineering Research Centre of Oil Shale Comprehensive Utilization, Ministry of Education, School of Energy and Power Engineering, Northeast Electric Power University, Province, Jilin, 132012, Jilin, China.

The co-combustion of sewage sludge and biomass is a key problem in coal-fired power plants. The combustion characteristics and pollutant emissions of municipal sewage sludge and biomass could result in unpredictable operation and environmental problems. In this study, the combustion experiments of corn stalk (CS), municipal sewage sludge (SS), and their blends were conducted in the thermogravimetric analyzer and muffle furnace, focusing on the combustion characteristics and the pollutants (SO/NO) emissions with different temperature, proportion, and heating rate. It was found that the combustion characteristics of the mixture are affected by the mix ratio of SS. Compared with those of SS, the SO emission amount and S-SO conversion rate of CS are lower. The content of N in SS is higher than CS, but the conversion rate of N-NO is lower. Although the emissions of SO and NO from CS blending with SS are higher than those from CS combustion alone, the conversion rate of SO and NO decreases. This means that the co-combustion of CS and SS will reduce the content of pollutants released by CS combustion alone and effectively solve the environmental problems associated with CS incineration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-11463-yDOI Listing
February 2021

BCL2 enhances survival of porcine pluripotent stem cells through promoting FGFR2.

Cell Prolif 2021 Jan 26;54(1):e12932. Epub 2020 Oct 26.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China.

Objectives: The establishment of porcine pluripotent stem cells (pPSCs) is still a critical topic. However, all pPSCs were failed to contribute to efficient chimeric pig and were extremely sensitive to changes of culture conditions. This study aimed to investigate the role of BCL2 in pPSCs and further explain the mechanism.

Materials And Methods: Porcine BCL2 gene was cloned and overexpressed in porcine induce pluripotent stem cells (piPSCs). Digital RNA-seq was performed to explain the mechanism of anti-apoptosis. Finally, the cells carrying BCL2 were injected into mouse early embryo to evaluate its chimeric ability.

Results: Here, we found that overexpression of porcine BCL2 gene significantly improved the survivability of piPSCs and the efficiency of embryonic chimerism, and did not wreck the pluripotency of piPSCs. Furthermore, the Digital RNA-seq analysis revealed that BCL2, as a downstream gene of the PI3K signal pathway, enhanced the expression of PI3K signal pathway receptors, such as FGFR2, and further promoted oxidoreductases activity and lipid metabolism, thus maintaining the survival and pluripotency of piPSCs.

Conclusion: Our data not only suggested that porcine BCL2 gene could enhance the survivability and chimeric ability of pPSCs, but also explained the positive feedback mechanism in this process, providing strong support for the chimeric experiment of pPSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.12932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791183PMC
January 2021

Tet2 regulates Barx2 expression in undifferentiated and early differentiated mouse embryonic stem cells.

Biochem Biophys Res Commun 2020 12 14;533(4):1212-1218. Epub 2020 Oct 14.

Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address:

The methylcytosine oxidase TET proteins play important roles in DNA demethylation and development. In developing embryos, TET2 are upregulated during pre-implantation development, and significantly expressed in the trophectoderm and inner cell mass. In this study, we identified Barx2 as a new target of Tet2. Tet2 bound and demethylated the promoter of Barx2 in mouse embryonic stem cells (mESCs) to maintain the expression of Barx2. During mESC differentiation, Tet2 bound the promoter of Barx2 in day 4 embryonic bodies but not in day 8 EBs. However, Barx2 expression remained unchanged. Thus, Tet2 functioned as a demethylase and maintained the expression of Barx2 in undifferentiated and early differentiated mESCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.09.095DOI Listing
December 2020

Single network double cross-linker (SNDCL) hydrogels with excellent stretchability, self-recovery, adhesion strength, and conductivity for human motion monitoring.

Soft Matter 2020 Aug;16(31):7323-7331

Yantai Institute of Materia Medica, Yantai, 264000, China.

Hydrogels, as a kind of soft materials, are good candidates for smart skin-like materials. A double network is usually fabricated to improve the mechanical properties of hydrogels, and involves two different kinds of networks. In this work, a novel strategy for preparing single network double cross-linker (SNDCL) hydrogels was proposed and the prepared hydrogels exhibited excellent mechanical properties, including stretchability, compressibility, self-recovery, adhesion, shape memory and mechanical strength. N,N'-Methylenebisacrylamide forms covalent bonds with the network, while citric acid can form multiple weak interactions due to the polycarboxylic structure. This improves the tensile properties (6564%) and compressive properties of the hydrogel, and the hydrogels also exhibit long-lasting self-adhesion ability on various substrates. In addition, the hydrogels with multiple properties can be used as flexible strain sensors, allowing the monitoring of body movements. The hydrogels can hopefully be used in wearable electronic sensor devices and for healthcare monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sm00375aDOI Listing
August 2020

Eif2s3y regulates the proliferation of spermatogonial stem cells via Wnt6/-catenin signaling pathway.

Biochim Biophys Acta Mol Cell Res 2020 10 1;1867(10):118790. Epub 2020 Jul 1.

College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering & Technology, Northwest A & F University, Yangling, Shaanxi, China. Electronic address:

Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked (Eif2s3y) gene, the gene encoding eIF2γ protein, is globally expressed in all tissues and plays important roles in regulating global and gene-specific mRNA translation initiation. It has been noticed that Eif2s3y plays crucial roles in spermatogenesis, however, the mechanism remains unclear. In the current study, transgenic Eif2s3y mice were generated to test our hypothesis that the Eif2s3y promotes the proliferation of spermatogonial stem cells (SSCs). Transgenic Eif2s3y mouse had enhanced SSCs proliferation rate when compared to WT mouse. Interesting, the testes from transgenic Eif2s3y mouse had increased Active-β-catenin protein expression and higher expression pattern of Wnt ligand Wnt6 when compared to testes from WT mouse. This study revealed novel roles of Eif2s3y in the activation Wnt6/β-catenin signal pathway in SSCs. Taken together, we identified Eif2s3y-Wnt6-β-catenin as a critical pathway in the regulation of spermatogenesis, which provides a platform for investigating the molecular mechanisms of male reproduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbamcr.2020.118790DOI Listing
October 2020

NCTD elicits proapoptotic and antiglycolytic effects on colorectal cancer cells via modulation of Fam46c expression and inhibition of ERK1/2 signaling.

Mol Med Rep 2020 Aug 18;22(2):774-782. Epub 2020 May 18.

Department of Oncology, Shanghai Traditional Chinese Medicine‑Integrated Hospital, Shanghai 200082, P.R. China.

Colorectal cancer is a digestive tract malignancy and the third leading cause of cancer‑related mortality worldwide. Norcantharidin (NCTD), the demethylated form of cantharidin, has been reported to possess anticancer properties. Family‑with‑sequence‑similarity‑46c (Fam46c), a non‑canonical poly(A) polymerase, has been reported to be critical in NCTD‑mediated effects in numerous types of cancer, including hepatoma. In the current study, it was found that Fam46c expression was reduced in colorectal cancer tissues and cells. Treatment with NCTD was observed to significantly enhance apoptosis and inhibit glycolysis in colorectal cancer cells. In addition, Fam46c and cleaved caspase 3 expression levels were found to be increased in response to NCTD treatment, in contrast to tumor‑specific pyruvate kinase M2 and phosphorylated ERK expression, which was reduced. Importantly, overexpression of Fam46c exerted similar effects as NCTD treatment on the apoptosis and glycolysis of colorectal cancer cells, whereas Fam46c knockdown strongly attenuated the effect of NCTD. Moreover, epidermal growth factor, which acts as an agonist of ERK1/2 signaling, weakened the effects of NCTD on colorectal cancer cells. Taken together, the results indicated that NCTD promotes apoptosis and suppresses glycolysis in colorectal cancer cells by possibly targeting Fam46c and inhibiting ERK1/2 signaling, hence suggesting that Fam46c may act as a tumor suppressor in colorectal cancer. Thus, the present study identified a novel therapeutic target of NCTD in the clinical treatment of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2020.11151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339822PMC
August 2020

Effects of Magnesium Oxide (MgO) Shapes on In Vitro and In Vivo Degradation Behaviors of PLA/MgO Composites in Long Term.

Polymers (Basel) 2020 May 8;12(5). Epub 2020 May 8.

School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China.

Biodegradable devices for medical applications should be with an appropriate degradation rate for satisfying the various requirements of bone healing. In this study, composite materials of polylactic acid (PLA)/stearic acid-modified magnesium oxide (MgO) with a 1 wt% were prepared through blending extrusion, and the effects of the MgO shapes on the composites' properties in in vitro and in vivo degradation were investigated. The results showed that the long-term degradation behaviors of the composite samples depended significantly on the filler shape. The degradation of the composites is accelerated by the increase in the water uptake rate of the PLA matrix and the composite containing the MgO nanoparticles was influenced more severely by the enhanced hydrophilicity. Furthermore, the pH value of the phosphate buffer solution (PBS) was obviously regulated by the dissolution of MgO through the neutralization of the acidic product of the PLA degradation. In addition, the improvement of the in vivo degrading process of the composite illustrated that the PLA/MgO materials can effectively regulate the degradation of the PLA matrix as well as raise its bioactivity, indicating the composites for utilization as a biomedical material matching the different requirements for bone-related repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym12051074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284841PMC
May 2020

Complex spatial patterns delay the discovery and location of food by rodents.

Integr Zool 2020 Jul 23;15(4):307-313. Epub 2020 Jun 23.

School of Life Sciences, Zhengzhou University, Gaoxin District, Zhengzhou, Henan Province, China.

Spatial patterns in heterogeneity are generally deemed a central causal factor influencing the physiology and behavior of animals in ecological systems. However, knowledge remains limited about how such patterns influence food discovery by animals. We inferred that spatial heterogeneity plays a key role in animal food discovery and location. To prove this inference, we tested food locating parameters by 2 rodent species, Apodemus agrarius and Lasiopodomys brandtii, in different heterogeneous environments. Our results showed that spatial heterogeneity significantly influenced the food locating time of rodents, with food locating time increasing with increasing spatial heterogeneity. Furthermore, spatial heterogeneity significantly influenced invalid excavations (digging in the wrong place). Finally, spatial heterogeneity significantly influenced the frequency that heterogeneous objects were explored. Supporting our inference, our results indicate that spatial heterogeneity significantly influences the foraging behavior of animals. Consequently, increased spatial heterogeneity will impair the food locating success of rodents. We believe that this work will broaden our understanding of plant-animal interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1749-4877.12429DOI Listing
July 2020

Living near the limits: Effects of interannual variation in food availability on diet and reproduction in a temperate primate, the Taihangshan macaque (Macaca mulatta tcheliensis).

Am J Primatol 2020 01 19;82(1):e23080. Epub 2019 Dec 19.

Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

Nutrient intake of animals is influenced by an interplay of external and internal factors, such as food availability and reproductive state, respectively. We used the nutritional geometry framework to analyze individual-based data on energy and nutrient intake in relation to reproductive state in a population of rhesus macaques (Macaca mulatta tcheliensis), which live in a harsh high-latitude habitat, the Taihangshan mountains of China, and exhibit strong reproductive seasonality. We combined data over a 3-year period on food availability, diets, reproductive output, and components of maternal investment to understand how Taihangshan macaques respond to variation in food availability and nutrition in reproduction. Our results show there was high interannual variation in availability of an important staple source of fat and carbohydrates (nonprotein energy), seeds of oak (Quercus spp). Despite this variability in seed availability skewing the dietary macronutrient ratios considerably (from 12.96% to 30.12% dietary energy from protein), total metabolizable energy intake was maintained across years during pregnancy. Lactating females had higher mean daily energy intakes than pregnant females. As in pregnant females, energy intake was maintained constant across years, but only when seed availability enabled the contribution of available protein to energy intake to be maintained between 15.32% (2013) and 17.97% (2015). In 2014, when seeds were scarce, lactating females had a shortfall in energy intake compared with 2013 and 2015. This corresponded with a reduction in the number of females giving birth (11 out of 23), but there was no interannual difference in survival rates. Compared to 2013 and 2015, in 2014 females had greater weight loss (drew on body reserves), moved less, and spent more time nursing their offspring. We discuss implications of these results for range limitation in Taihangshan macaques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajp.23080DOI Listing
January 2020

MicroRNA-98-5p regulates the proliferation and apoptosis of A549 cells by targeting MAP4K3.

Oncol Lett 2019 Oct 22;18(4):4288-4293. Epub 2019 Aug 22.

Department of Medical Oncology, General Hospital of Xuzhou Mining Group, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China.

Non-small cell lung cancer (NSCLC) is a primary subtype of lung cancer that is accompanied by a high incidence rate and poor prognosis. The primary treatment for NSCLC is chemotherapy, which has low effectiveness and high toxicity. Thus, novel targeted therapy has drawn much attention in recent years. MicroRNAs (miRs) serve important roles in multiple cancer types. In the current study, a decrease in miR-98-5p and an increase in mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) was observed in NSCLC tumor tissues compared with normal tissues. miR-98-5p was predicted to target positions 1,056-1,063 of the MAP4K3 3'-untranslated region (UTR). The binding sites between miR-98-5p and the 3'-UTR of MAP4K3 messenger RNA were supported by the results of a dual-luciferase reporter assay. Compared with the control and miR-negative control (NC) groups, miR-98-5p mimic significantly reduced cell proliferation and increased apoptosis in NSCLC cells. In addition, miR-98-5p mimic reduced the expression of MAP4K3 and mammalian target of rapamycin while increasing the expression of cleaved caspase-3 compared with the control group and miR-NC groups. In conclusion, miR-98-5p may inhibit the progression of NSCLC via targeting of MAP4K3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2019.10771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757256PMC
October 2019

ETS1 targets RYBP transcription to inhibit tumor cell proliferation.

Biochem Biophys Res Commun 2019 02 10;509(3):810-816. Epub 2019 Jan 10.

Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. Electronic address:

ETS1 (E26 transformation specific-1) is the founding member of ETS transcriptional factor family. It transcriptionally modulates numerous gene expressions, and is involved in cellular differentiation, tissue remodeling, angiogenesis, drug resistance and tumorigenesis. ETS1 is usually regarded as an oncogene. However, its apoptosis-inducing activity was also frequently reported. Here, we identified RYBP (Ring1 and YY1 binding protein), a critical epigenetic regulator and apoptosis enhancer, as a novel transcriptional target of ETS1. Specifically, we found that overexpression of ETS1 up-regulates the promoter activity of RYBP in HEK293T and tumor cells from different tissue origins, indicating a universal transcriptional regulatory effect. Subsequently, both overexpression and RNA interfering experiments demonstrated that ETS1 positively modulates RYBP expression from both mRNA and protein levels. Bioinformatics analysis combined with site-directed mutagenesis suggested that there probably exist a multiple of ETS1 binding sites in RYBP promoter region, and chromatin immunoprecipitation assay validates the physical association between ETS1 protein and RYBP promoter region. Functional studies showed that ectopic expression of ETS1 significantly suppresses tumor cell proliferation. However, this inhibitory effect was partially compromised when RYBP was concomitantly knocked down by its specific short hairpin RNA. Meanwhile, we provide evidence to demonstrate that cyclin-dependent kinase inhibitor p21 is possibly involved in this regulatory loop. Taken together, our current study identified RYBP as a new transcriptional target which is utilized by ETS1 to carry out its tumor cell growth inhibitory effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2019.01.006DOI Listing
February 2019
-->