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1.
Chinese Journal of Medical Genetics ; (6): 887-891, 2023.
Article in Chinese | WPRIM | ID: wpr-981842

ABSTRACT

The GATOR1 complex is located at the upstream of the mTOR signal pathway and can regulate the function of mTORC1. Genetic variants of the GATOR1 complex are closely associated with epilepsy, developmental delay, cerebral cortical malformation and tumor. This article has reviewed the research progress in diseases associated with genetic variants of the GATOR1 complex, with the aim to provide a reference for the diagnosis and treatment of such patients.


Subject(s)
Humans , GTPase-Activating Proteins/metabolism , Signal Transduction/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Epilepsy/genetics , Neoplasms
2.
Chinese Journal of Biotechnology ; (12): 4796-4808, 2023.
Article in Chinese | WPRIM | ID: wpr-1008059

ABSTRACT

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.


Subject(s)
Animals , Swine , African Swine Fever Virus/metabolism , Membrane Proteins/metabolism , Immunity, Innate , Nucleotidyltransferases/metabolism , Signal Transduction/genetics
3.
Asian Journal of Andrology ; (6): 737-744, 2023.
Article in English | WPRIM | ID: wpr-1009787

ABSTRACT

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.


Subject(s)
Humans , Male , Young Adult , Adult , Middle Aged , MicroRNAs/genetics , Signal Transduction/genetics , Spermatozoa/metabolism , Gene Expression Profiling
4.
Chinese Journal of Cellular and Molecular Immunology ; (12): 1141-1145, 2023.
Article in Chinese | WPRIM | ID: wpr-1009466

ABSTRACT

DNA sensor, a kind of pattern recognition receptor (PRR), is widely expressed in innate immune cells. It activates the inflammatory signaling pathways and triggers an innate immune response by recognizing the pathogens or DNA in abnormal host cells. DNA-dependent activator of IFN-regulatory factors (DAI) is the first cytoplasmic DNA receptor discovered, which plays an important role in regulating the innate immune responses characterized by induction of interferon and programmed cell death. The article summarizes the molecular characteristics of DAI, its downstream signaling pathways, and its role and mechanism in anti-infective immunity, tumor immunity and inflammatory diseases. It also makes a preliminary exploration of the correlation between DAI and transplantation immunology, and provides a new target for the therapy of various immune diseases.


Subject(s)
DNA/metabolism , Receptors, Pattern Recognition , Immunity, Innate , Signal Transduction/genetics , DNA-Binding Proteins/genetics
5.
Protein & Cell ; (12): 238-261, 2023.
Article in English | WPRIM | ID: wpr-982533

ABSTRACT

Neurons migrate from their birthplaces to the destinations, and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners. These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short- and long-range cell-cell communications. Neuronal guidance genes (encoding cues, receptors, or downstream signal transducers) are critical not only for development of the nervous system but also for synaptic maintenance, remodeling, and function in the adult brain. One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes, including neuronal migration, axonal guidance, synaptogenesis, and circuit formation. Importantly, neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system. We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases, ranging from developmental, neuropsychiatric, and neurodegenerative disorders to cancer metastasis. We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases. Furthermore, we discuss the remaining challenges and therapeutic potentials of modulating neuronal guidance pathways in neural repair.


Subject(s)
Humans , Axon Guidance/genetics , Neurons , Axons/metabolism , Signal Transduction/genetics , Cell Communication
6.
Protein & Cell ; (12): 513-531, 2023.
Article in English | WPRIM | ID: wpr-982530

ABSTRACT

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.


Subject(s)
Humans , Animals , Mice , Adaptor Proteins, Signal Transducing/metabolism , Transcription Factors/metabolism , Stomach Neoplasms/pathology , Neutrophils/pathology , Signal Transduction/genetics , YAP-Signaling Proteins , Tumor Microenvironment , Hyaluronan Receptors/genetics
7.
Journal of Central South University(Medical Sciences) ; (12): 516-525, 2023.
Article in English | WPRIM | ID: wpr-982318

ABSTRACT

OBJECTIVES@#Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism.@*METHODS@#A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children.@*RESULTS@#After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05].@*CONCLUSIONS@#The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.


Subject(s)
Child , Infant, Newborn , Humans , Female , Pediatric Obesity/genetics , Sterol Regulatory Element Binding Protein 1 , Premature Birth , Non-alcoholic Fatty Liver Disease , Signal Transduction/genetics , Insulins
8.
Journal of Zhejiang University. Science. B ; (12): 50-63, 2023.
Article in English | WPRIM | ID: wpr-971468

ABSTRACT

Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.


Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Cell Hypoxia , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/pathology , Signal Transduction/genetics , tRNA Methyltransferases/metabolism
9.
China Journal of Orthopaedics and Traumatology ; (12): 194-198, 2022.
Article in Chinese | WPRIM | ID: wpr-928293

ABSTRACT

Spinal cord injury is a severe central nervous system disease, which will cause a series of complex pathophysiological changes and activate a variety of signaling pathways including Notch signaling. Studies have evidenced that activation of the Notch signaling pathway is not conducive to nerve repair and symptom improvement after spinal cord injury. Its mechanisms include inhibiting neuronal differentiation and axon regeneration, promoting reactive astrocyte proliferation, promoting M1 macrophage polarization and the release of proinflammatory factors, and inhibiting angiogenesis. Therefore, it has become a promising therapeutic strategy to inhibit Notch signal as a target in the treatment of spinal cord injury. In recent years, some researchers have used drugs, cell transplantation or genetic modification to regulate Notch signaling, which can promote the recovery of nerve function after spinal cord injury, thereby providing new treatment strategies for the treatment of spinal cord injury. This article will summarize the mechanism of Notch signaling pathway in spinal cord injury, and at the same time review the research progress in the treatment of spinal cord injury by modulating Notch signaling pathway in recent years, so as to provide new research ideas for further exploring new strategies for spinal cord injury.


Subject(s)
Humans , Axons/metabolism , Cell Transplantation , Nerve Regeneration , Signal Transduction/genetics , Spinal Cord/metabolism , Spinal Cord Injuries/metabolism
10.
Chinese Medical Journal ; (24): 2465-2474, 2021.
Article in English | WPRIM | ID: wpr-921151

ABSTRACT

BACKGROUND@#Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.@*METHODS@#BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.@*RESULTS@#In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.@*CONCLUSION@#UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.


Subject(s)
Female , Humans , Biomarkers, Tumor , Breast Neoplasms/pathology , Cell Proliferation/genetics , Computational Biology , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/genetics , TOR Serine-Threonine Kinases/genetics , Ubiquitin-Conjugating Enzymes/metabolism
11.
Chinese Journal of Biotechnology ; (12): 1260-1276, 2021.
Article in Chinese | WPRIM | ID: wpr-878629

ABSTRACT

The unicellular green alga Haematococcus pluvialis is the best source of natural astaxanthin (AST) in the world due to its high content under stress conditions. Although high light (HL) can effectively induce AST biosynthesis, the specific mechanisms of light signal perception and transduction are unclear. In the current study, we used transcriptomic data of normal (N), high white light (W), and high blue light (B) to study the mechanisms of light inducing AST accumulation from the point of photoreceptors. The original data of 4.0 G, 3.8 G, and 3.6 G for N, W, and B were obtained, respectively, by the Illumina Hi-seq 2000 sequencing technology. Totally, 51 954 unigenes (at least 200 bp in length) were generated, of which, 20 537 unigenes were annotated into at least one database (NR, NT, KO, SwissProt, Pfam, GO, or KOG). There were 1 255 DEGs in the W vs N, 1 494 DEGs in the B vs N, and 1 008 DEGs in the both W vs N and B vs N. KEGG enrichment analysis revealed that photosynthesis, oxidative phosphorylation, carotenoid biosynthesis, fatty acids biosynthesis, DNA replication, nitrogen metabolism, and carbon metabolism were the significantly enriched pathways. Moreover, a large number of genes encoding photoreceptors and predicted interacting proteins were predicted in Haematococcus transcriptome data. These genes showed significant differences at transcriptional expression levels. In addition, 15 related DEGs were selected and tested by qRT-PCR and the results were significantly correlated with the transcriptome data. The above results indicate that the signal transduction pathway of "light signal - photoreceptors - interaction proteins - (interaction proteins - transcription factor/transcriptional regulator) - gene expression - AST accumulation" might play important roles in the regulation process, and provide reference for further understanding the transcriptional regulation mechanisms of AST accumulation under HL stress.


Subject(s)
Chlorophyta/genetics , Gene Expression Profiling , Signal Transduction/genetics , Transcriptome/genetics , Xanthophylls
12.
Rev. cuba. invest. bioméd ; 39(4): e604, oct.-dic. 2020. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156461

ABSTRACT

La insuficiencia cardiaca se define como un síndrome caracterizado por la incapacidad de proveer las necesidades metabólicas del organismo, presentando disnea y fatiga. Hasta ahora, se ha descrito la participación de varias moléculas involucradas en los mecanismos de señalización intracelular que conducen a la insuficiencia cardiaca y estimulan la síntesis de algunas proteínas, como colágeno, la cual induce a una hipertrofia cardiaca(AU)


Heart failure is defined as a syndrome characterized by the inability to meet the metabolic needs of the organism, causing dyspnea and fatigue.Descriptions are available of the involvement of several molecules in cell signaling mechanisms which lead to heart failure and prompt the synthesis of some proteins, such as collagen, inducing cardiac hypertrophy(AU)


Subject(s)
Humans , Heart Failure/genetics , Molecular Biology , Angiotensins/therapeutic use , Signal Transduction/genetics , Cardiomegaly/complications
13.
J. coloproctol. (Rio J., Impr.) ; 40(2): 135-142, Apr.-Jun. 2020. tab, graf, ilus
Article in English | LILACS | ID: biblio-1134976

ABSTRACT

ABSTRACT Colorectal cancer is one of the most important malignancies in the classification of gastrointestinal cancers. One of the predisposing factors at molecular level for this cancer is via WNT signaling which is associated with the vast numbers of different genes. Thus, in this study, we aimed to investigate whether Adenomatous Polyposis Coli gene (APC) mutation of rs41115in two locations such as 132.002 and 131.989 acts as a trigger or cause of colorectal cancer. Relatively, 30 blood samples of colorectal cancer patients and 30 normal blood samples as control group after colonoscopy and also confirmation of pathology report at Rohani Hospital in Babol (Iran) were investigated. The primers were designed in order to be included the rs41115 to identify the particular polymorphisms of gene. The polymerase chain reaction (PCR direct sequencing method) was used. Conclusively, deletion of adenine in two specific locations such as 131.989 and 132.002 has been identified, but there was no relationship between rs41115 polymorphisms located in adenomatous polyposis coli gene and colorectal cancer.


RESUMO O câncer colorretal é uma das neoplasias malignas mais importantes na classificação dos cânceres gastrointestinais. Um dos fatores predisponentes no âmbito molecular para esse câncer é através da via de sinalização WNT, que está associada a um grande número de genes diferentes. Portanto, neste estudo, objetivamos investigar se a mutação rs41115 do gene da polipose adenomatosa do cólon (Adenomatous Polyposis Coli - APC) em dois locais como 132.002 e 131.989 atua como gatilho ou como causa do câncer colorretal. Relativamente, 30 amostras de sangue de pacientes com câncer colorretal e 30 amostras de sangue normal (grupo controle) foram analisadas após a colonoscopia, bem como a confirmação do laudo da patologia no Rohani Hospital em Babol (Irã). Os primers foram projetados de modo a incluir o rs41115 para identificar os polimorfismos particulares do gene. A reação em cadeia da polimerase (método de sequenciamento direto por PCR) foi utilizada. Conclusivamente, a deleção de adenina em dois locais específicos, como 131.989 e 132.002, foi identificada, mas não houve relação entre o polimorfismo rs41115 localizado no gene da polipose adenomatosa do cólon e o câncer colorretal.


Subject(s)
Humans , Male , Female , Polymorphism, Genetic , Colorectal Neoplasms/pathology , Genes, APC , Adenine , Signal Transduction/genetics , Polymerase Chain Reaction , Colonoscopy , Adenomatous Polyposis Coli/pathology
14.
Asian Journal of Andrology ; (6): 162-168, 2020.
Article in English | WPRIM | ID: wpr-1009742

ABSTRACT

Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.


Subject(s)
Adult , Aged , Humans , Male , Middle Aged , A Kinase Anchor Proteins/genetics , Biomarkers, Tumor/genetics , China , Cytoskeletal Proteins/genetics , DNA-Binding Proteins/genetics , Gene Amplification , High-Throughput Nucleotide Sequencing , Homeodomain Proteins/genetics , Mutation , Neoplasm Proteins/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Mas , Receptors, Androgen/genetics , Signal Transduction/genetics , Zinc Finger Protein GLI1/genetics
15.
Chinese Medical Sciences Journal ; (4): 20-30, 2020.
Article in English | WPRIM | ID: wpr-1008962

ABSTRACT

Objective To discover critical genes contributing to the stemness and maintenance of spermatogonial stem cells (SSCs) and provide new insights into the function of the leucine-rich repeat (LRR) family member Lrrc34 (leucine-rich repeat-containing 34) in SSCs from mice. Methods Bioinformatic methods, including differentially expressed gene (DEG), gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were used to uncover latent pluripotency-related genes. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence analyses were utilized to verify the mRNA and protein expression levels, respectively. RNA interference of Lrrc34 using siRNA was performed to detect its transient impact on SSCs. Results Eight DEGs between ID4-EGFP+ (G) and ID4-EGFP+/TSPAN8High (TH), eight DEGs between G and ID4-EGFP+/TSPAN8Low (TL) and eleven DEGs between TH and TL were discovered, and eleven protein-protein interaction (PPI) modules were found to be significant in the PPI network of DEGs. One of the DEGs, Lrrc34, was selected as a potential pluripotency-related gene due to its differential expression among ID4-EGFP+ spermatogonia subsets and its interaction with fibroblast growth factor 2 in the fifth module. Immunofluorescence experiments exhibited specific expression of Lrrc34 in a subpopulation of undifferentiated spermatogonia marked by LIN28A, and RT-PCR experiments confirmed the high expression of Lrrc34 in SSCs from P7 and adult mice. The transient knockdown of Lrrc34 in SSCs resulted in reduced colony sizes and significant changes in the transcriptome and apoptotic pathways. Conclusion Lrrc34 is highly expressed in mouse SSCs and is required for SSC proliferation in vitro through effects on transcriptome and signaling transduction pathways.


Subject(s)
Animals , Humans , Male , Apoptosis/genetics , Cell Proliferation/genetics , Cells, Cultured , Gene Expression Profiling/methods , Gene Ontology , Gene Regulatory Networks , Mice, Inbred C57BL , Mice, Transgenic , RNA Interference , Repressor Proteins/metabolism , Signal Transduction/genetics , Stem Cells/metabolism
16.
Journal of Zhejiang University. Science. B ; (12): 1-8, 2019.
Article in English | WPRIM | ID: wpr-1010438

ABSTRACT

Cancer remains a serious healthcare problem despite significant improvements in early detection and treatment approaches in the past few decades. Novel biomarkers for diagnosis and therapeutic strategies are urgently needed. In recent years, long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in tumors and show crosstalk with key cancer-related signaling pathways. In this review, we summarized the current progress of research on cytoplasmic lncRNAs and their roles in regulating cancer signaling and tumor progression, further characterization of which may lead to effective approaches for cancer prevention and therapy.


Subject(s)
Animals , Humans , Biomarkers, Tumor/metabolism , Cytoplasm/metabolism , Hippo Signaling Pathway , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/metabolism , Signal Transduction/genetics
17.
Asian Journal of Andrology ; (6): 508-515, 2019.
Article in English | WPRIM | ID: wpr-1009689

ABSTRACT

The aim of this study was to investigate the mechanism by which a diet inducing high hyperhomocysteinemia (HHcy) leads to the deterioration of erectile function in rats and whether this is inhibited by expression of the human tissue kallikrein-1 (hKLK1) gene. We established a rat model of HHcy by feeding methionine (Met)-rich diets to male Sprague-Dawley (SD) rats. Male wild-type SD rats (WTRs) and transgenic rats harboring the hKLK1 gene (TGRs) were fed a normal diet until 10 weeks of age. Then, 30 WTRs were randomly divided into three groups as follows: the control (n = 10) group, the low-dose (4% Met, n = 10) group, and the high-dose (7% Met, n = 10) group. Another 10 age-matched TGRs were fed the high-dose diet and designated as the TGR+7% Met group. After 30 days, in all four groups, erectile function was measured and penile tissues were harvested to determine oxidative stress, endothelial cell content, and penis fibrosis. Compared with the 7% Met group, the TGR+7% Met group showed diminished HHcy-induced erectile dysfunction (ED), indicating the improvement caused by hKLK1. Regarding corpus cavernosum endothelial cells, hKLK1 preserved endothelial cell-cell junctions and endothelial cell content, and activated protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) signaling. Fibrosis assessment indicated that hKLK1 preserved normal penis structure by inhibiting apoptosis in the corpus cavernosum smooth muscle cells. Taken together, these findings showed that oxidative stress, impaired corpus cavernosum endothelial cells, and severe penis fibrosis were involved in the induction of ED by HHcy in rats, whereas hKLK1 preserved erectile function by inhibiting these pathophysiological changes.


Subject(s)
Animals , Humans , Male , Rats , Apoptosis , Diet , Endothelial Cells , Erectile Dysfunction/prevention & control , Fibrosis , Hyperhomocysteinemia/complications , Methionine , Oxidative Stress , Penis/pathology , Rats, Sprague-Dawley , Rats, Transgenic , Signal Transduction/genetics , Tissue Kallikreins/genetics
18.
Asian Journal of Andrology ; (6): 233-240, 2019.
Article in English | WPRIM | ID: wpr-1009650

ABSTRACT

Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.


Subject(s)
Humans , Male , Androgen Antagonists/therapeutic use , Cell Differentiation/genetics , Disease Progression , Neoplastic Stem Cells/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms, Castration-Resistant/pathology , Signal Transduction/genetics
19.
Braz. j. med. biol. res ; 51(1): e6698, 2018. tab, graf
Article in English | LILACS | ID: biblio-889006

ABSTRACT

Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.


Subject(s)
Humans , Spondylitis, Ankylosing/genetics , Signal Transduction/genetics , Gene Expression , Receptor Cross-Talk/physiology , Gene Expression Profiling/methods , Reference Values , Monte Carlo Method , Area Under Curve , Databases, Genetic , Microarray Analysis/methods , Genetic Association Studies
20.
Biol. Res ; 51: 46, 2018. tab, graf
Article in English | LILACS | ID: biblio-983950

ABSTRACT

The negative effects of environmental stresses, such as low temperature, high temperature, salinity, drought, heavy metal stress, and biotic stress significantly decrease crop productivity. Plant hormones are currently being used to induce stress tolerance in a variety of plants. Brassinosteroids (commonly known as BR) are a group of phytohormones that regulate a wide range of biological processes that lead to tolerance of various stresses in plants. BR stimulate BRASSINAZOLE RESISTANCE 1 (BZR1)/BRI1-EMS SUPPRESSOR 1 (BES1), transcription factors that activate thousands of BR-targeted genes. BR regulate antioxidant enzyme activities, chlorophyll contents, photosynthetic capacity, and carbohydrate metabolism to increase plant growth under stress. Mutants with BR defects have shortened root and shoot developments. Exogenous BR application increases the biosynthesis of endogenous hormones such as indole-3-acetic acid, abscisic acid, jasmonic acid, zeatin riboside, brassinosteroids (BR), and isopentenyl adenosine, and gibberellin (GA) and regulates signal transduction pathways to stimulate stress tolerance. This review will describe advancements in knowledge of BR and their roles in response to different stress conditions in plants.


Subject(s)
Stress, Physiological/physiology , Transcription Factors/genetics , Signal Transduction/genetics , Gene Expression Regulation, Plant/genetics , Brassinosteroids/metabolism , Stress, Physiological/genetics , Signal Transduction/physiology , Gene Expression Regulation, Plant/physiology
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