ABSTRACT
The citrus cultivar 'Local Juhong', which has historically been used as a traditional Chinese medicinal material, originated in Yuanjiang County, Hunan Province.Its parental type and genetic background are indistinct as of yet. Morphological observation shows that 'Local Juhong' has a slight oblateness in fruit shape, a relatively smooth pericarp, a fine and slightly raised oil vacuole, and an inward concave at the blossom end. The tree form and fruit and leaf morphology of 'Local Juhong' are similar to those of 'Huangpi' sour orange. To reveal the genetic background of 'Local Juhong', 21 citrus accessions were evaluated using nuclear and chloroplast SSR markers and whole-genome SNP information. 'Local Juhong' was grouped with mandarins and sub-grouped with 'Miyagawa Wase' and 'Yanxi Wanlu' in a nuclear SSR analysis, which indicated that its pollen parent might be mandarins. It was closely clustered with orange and pummelo in the chloroplast SSR analysis. The genomic sequence similarity rate of 'Local Juhong' with mandarin and pummelo heterozygosity was 70.88%; the main part was the heterozygosity, except for the unknown (19.66%), mandarin (8.73%), and pummelo (3.9%) parts. Thus, 'Local Juhong' may be an F1 hybrid with pummelo as the female parent and mandarin as the male parent, sharing sisterhood with 'Huangpi' sour orange.
Subject(s)
Citrus , Microsatellite Repeats , Citrus/genetics , Microsatellite Repeats/genetics , Polymorphism, Single Nucleotide , Plants, Medicinal/genetics , Genomics/methods , Genome, Plant , Genetic Markers , Phylogeny , Chloroplasts/geneticsABSTRACT
Although revisiting the discoveries and implications of genetic variations using phased genomics is critical, such efforts are still lacking. Somatic mutations represent a crucial source of genetic diversity for breeding and are especially remarkable in heterozygous perennial and asexual crops. In this study, we focused on a diploid sweet orange (Citrus sinensis) and constructed a haplotype-resolved genome using high fidelity (HiFi) reads, which revealed 10.6% new sequences. Based on the phased genome, we elucidate significant genetic admixtures and haplotype differences. We developed a somatic detection strategy that reveals hidden somatic mutations overlooked in a single reference genome. We generated a phased somatic variation map by combining high-depth whole-genome sequencing (WGS) data from 87 sweet orange somatic varieties. Notably, we found twice as many somatic mutations relative to a single reference genome. Using these hidden somatic mutations, we separated sweet oranges into seven major clades and provide insight into unprecedented genetic mosaicism and strong positive selection. Furthermore, these phased genomics data indicate that genomic heterozygous variations contribute to allele-specific expression during fruit development. By integrating allelic expression differences and somatic mutations, we identified a somatic mutation that induces increases in fruit size. Applications of phased genomics will lead to powerful approaches for discovering genetic variations and uncovering their effects in highly heterozygous plants. Our data provide insight into the hidden somatic mutation landscape in the sweet orange genome, which will facilitate citrus breeding.
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In this study, considering the combined effects of atmospheric attenuation and turbulence, we examine the spot quality and spatial intensity distribution characteristics of a supercontinuum (SC) laser propagating in a turbulent atmosphere using the multi-layer phase-screen method. An increase in turbulence strength or a decrease in the initial beam radius resulted in a greater impact of the atmospheric turbulence on the SC laser. A decrease in source coherence results in the deterioration of the image quality of the far-field spot. Under moderate to strong turbulence, the scintillation index decreased as the source coherence decreased; however, the opposite trend was observed under weak turbulence. These results are significant for the advancement and optimization of SC laser systems.
ABSTRACT
As an important part of the ecological environment, degraded coastal soils urgently require efficient and eco-friendly soil amendment. Biochar and wood vinegar have been proved to be effective soil amendments, and acid-modified biochar has great potential in ameliorating the degraded coastal saline-alkali soil. However, the effects of individual or combined application of biochar (BC), acid-modified biochar (ABC), and wood vinegar (WV) on coastal saline-alkali soil are unknown. Hence, biochar, wood vinegar, and acid-modified biochar were prepared by pyrolysis of poplar wood. The properties of biochar were characterized, and soil incubation experiments were conducted. The results showed that ABC decreased the soil alkalinity by acid-base neutralization and improved the soil fertility by increasing the nutrients (C, N, P). ABC provided a more suitable environment and changed the abundance and diversity of soil microorganisms. ABC increased the relative contents of specific families (e.g., Pseudomonadaceae and Sphingomonadaceae), which had strong ecological linkages in the C, N, and P cycles and organic matter degradation. The results indicated that WV had little effect on coastal saline-alkali soil, whereas individual and combined application of biochar (especially ABC) showed an efficient remediation effect. Our preliminary study demonstrated that the ABC could be a suitable solution for ameliorating degraded coastal saline-alkali soils.
Subject(s)
Charcoal , Soil , Acetic Acid , Acids , Alkalies , Humans , Methanol , NutrientsABSTRACT
Patients with asthenozoospermia often present multiple defects in sperm functions apart from a decrease in sperm motility. However, the etiological factors underlying these multifaceted defects remain mostly unexplored, which may lead to unnecessary treatment and unsatisfactory assisted reproductive technologies (ART) outcome. Here, we show that the protein levels of CD147 were lowered in sperm obtained from asthenozoospermic infertile patients exhibiting defects in both sperm motility and the acrosome reaction. Whereas CD147 maintained sperm motility before capacitation, female tract-derived soluble CD147 interacted with sperm-bound CD147 to induce an acrosome reaction in capacitated sperm. Soluble CD147 treatment restored the acrosome reaction and improved the fertility of sperm from patients with asthenozoospermia. Mechanistically, CD147 promotes sperm motility and acrosome reaction (AR) by eliciting Ca2+ influx through soluble CD147 binding to sperm-bound CD147. Notably, the level of soluble CD147 in seminal plasma was positively correlated with the fertilization rate and pregnancy outcome in infertile couples undergoing in vitro fertilization. Our study has identified a marker for the diagnosis and a therapeutic target for the defective AR capability in asthenozoospermia and a candidate for the prediction of in vitro fertilization outcomes for male infertile patients that facilitates the development of precision medicine in ART.
ABSTRACT
Endocrine therapy for prostate cancer (PCa) mainly inhibits androgen receptor (AR) signaling, due to increased androgen synthesis and AR changes, PCa evolved into castration-resistant prostate cancer (CRPC). The function of Family With Sequence Similarity 64 Member A (FAM64A) and its association with prostate cancer has not been reported. In our research, we first reported that FAM64A is up-regulated and positively associated with poor prognosis of patients with prostate cancer (PCa) by TCGA database and immunohistochemistry staining. Moreover, knockdown of FAM64A significantly suppressed the proliferation, migration, invasion, and cell cycle of PCa cells in vitro. Mechanistically, FAM64A expression was increased by dihydrotestosterone (DHT) through direct binding of AR to FAM64A promoter, and notably promoted the proliferation, migration, invasion, and cell cycle of androgen-dependent cell line of PCa. In addition, abnormal expression of FAM64A affects the immune and interferon signaling pathway of PCa cells. In conclusion, FAM64A was up-regulated by AR through directly binding to its specific promoter region to promote the development of PCa, and was associated with the immune mechanism and interferon signaling pathway, which provided a better understanding and a new potential for treating PCa.
Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Nuclear Proteins/metabolism , Prostatic Neoplasms/metabolism , Receptors, Androgen/metabolism , Binding Sites , Cell Cycle , Cell Movement , Cell Proliferation , Databases, Genetic , Gene Expression Regulation, Neoplastic , Humans , Interferons/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Neoplasm Invasiveness , Nuclear Proteins/genetics , PC-3 Cells , Promoter Regions, Genetic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology , Receptors, Androgen/genetics , Signal Transduction , Up-RegulationABSTRACT
Neonicotinoid and fipronil insecticides have been consumed worldwide, particularly in China. There is growing interest in the environmental research community about the occurrence, sources, and risks of neonicotinoids and fipronil. A new method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and disc solid phase extraction (SPE) techniques were developed for the determination of neonicotinoids and fipronil in seawater in this research. The effects of the styrene divinyl benzene-reverse phase sulfonated (SDB-RPS) membrane-based solid phase extraction optimization process and the HPLC separation parameters on the detection results of the target compounds were studied. Under the optimized conditions, the detection limit of this method for 12 target compounds ranged from 0.05 ng L-1 to 0.50 ng L-1 and absolute recovery was achieved from 58.9-106.5%. The results proved that this method can effectively detect neonicotinoid and fipronil pesticides in seawater. At the same time, dinotefuran, nitenpyram, thiamethoxam, imidacloprid, thiacloprid, fipronil and its metabolites were found in seawater samples from the Yangtze River Estuary and the adjacent sea area. Among them, the total concentration of neonicotinoid insecticides ranged from ND-12.45 ng L-1 and the average total concentration was 3.5 ng L-1; the total concentration of fipronil and its metabolites ranged from ND-2.45 ng L-1, and the average total concentration was 0.79 ng L-1. The results showed that there was contamination of neonicotinoids and fipronil in the Yangtze River Estuary and its adjacent area.
ABSTRACT
BACKGROUND: Renal cell carcinoma (RCC) is one of the most common tumors in urinary tract tumors. However, the mechanism that supports renal cell carcinoma is unclear. The function of transcription elongation factor A (SII)-like 2 (TCEAL2) and its association with human cancer have not been reported. MATERIALS AND METHODS: To explore the role of TCEAL2 in carcinogenesis of clear cell renal cell carcinoma (ccRCC), we performed bioinformatics analysis to determine the expression levels of TCEAL2 in ccRCC specimens and normal kidney tissue and then verified findings with our samples by qPCR, Western blot and immunohistochemistry staining. Furthermore, the lentiviral vectors were used to increase the expression of TCEAL2 in ccRCC cell lines. The immunofluorescence assay was taken to observe the subcellular location of TCEAL2 in ccRCC cells, and CCK-8 and flow cytometry were introduced for assessing cell proliferation and cell cycle of ccRCC cells, respectively. RESULTS: Compared with adjacent normal kidney tissue and human proximal tubular epithelial cells, the expression of TCEAL2 in ccRCC tissues and cell lines was down-regulated. Patients who had low expression of TCEAL2 had a statistically significant late tumor stage. Restore of TCEAL2 in ccRCC cells inhibited cell proliferation and induced cell cycle arrest in S phase of ccRCC cells. CONCLUSION: To our knowledge, this is the first report of TCEAL2 expression changes in ccRCC. We found that the decrease of TCEAL2 expression may be related to the occurrence of ccRCC. Further research is needed to clarify the molecular mechanism of TCEAL2 in progress of ccRCC.
ABSTRACT
INTRODUCTION: Obstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but the relatively independent polysomnography (PSG) outcomes of apnea and nocturnal hypoxia may not effectively assess the physiological impairment of OSA well. AIM: To propose a new calculation method, the blood oxygen accumulation distribution area index (BOADAI), for evaluating the association between OSA and ED. METHODS: In this study, 502 male participants with suspected OSA were enrolled. Clinical questionnaire, physical measurements, and PSG outcomes were obtained by 2 respiratory physicians. ED was assessed by a urologist using the International Index of Erectile Function-5 (IIEF-5). Whole pulse oxygen saturation curves during the sleep time were compressed into a fixed scale image, and the distribution area of oxygen saturation curves was outlined. We then calculated the value of the outlined area and normalized it by total sleep time. The least absolute shrinkage and selection operator logistic regression model was used for selecting the optimal variable associated with ED and model construction. The clinical net benefit of the BOADAI and its related modules was estimated and compared by decision curve analysis. MAIN OUTCOME MEASURE: ED and OSA were assessed using the IIEF-5, clinical questionnaire, physical measurements, and PSG outcomes. RESULTS: The frequency of ED in patients with OSA was significantly greater than that in the no-OSA group. Meanwhile, the new BOADAI was negatively correlated with the IIEF-5 score (r = -0.2525, P = .0000). Moreover, the least absolute shrinkage and selection operator method retained BOADAI but not the other PSG parameters such as respiratory disorder index and lowest SaO2. Finally, logistic regression analysis revealed that older age, lips with cyanochroia, systemic hypertension, and BOADAI were independently associated with ED, and decision curve analysis indicated the clinical usefulness of the BOADAI module. CONCLUSION: This study revealed novel evidence that OSA is a risk factor for ED. Meanwhile, the BOADAI could act as a potential clinical characteristic to evaluate ED in patients with OSA and to provide clinical treatment recommendations. Zheng W, Chen X, Huang J, et al. Blood Oxygen Accumulation Distribution Area Index Is Associated With Erectile Dysfunction in Patients With Sleep Apnea-Results From a Cross-sectional Study. Sex Med 2019; 8:36-44.
ABSTRACT
Alternative splicing (AS) constitutes a major reason for messenger RNA (mRNA) and protein diversity. Increasing studies have shown a link to splicing dysfunction associated with malignant neoplasia. Systematic analysis of AS events in kidney cancer remains poorly reported. Therefore, we generated AS profiles in 533 kidney renal clear cell carcinoma (KIRC) patients in The Cancer Genome Atlas (TCGA) database using RNA-seq data. Then, prognostic models were developed in a primary cohort (N = 351) and validated in a validation cohort (N = 182). In addition, splicing networks were built by integrating bioinformatics analyses. A total of 11 268 and 8083 AS variants were significantly associated with patient overall survival time in the primary and validation KIRC cohorts, respectively, including STAT1, DAZAP1, IDS, NUDT7, and KLHDC4. The AS events in the primary KIRC cohorts served as candidate AS events to screen the independent risk factors associated with survival in the primary cohort and to develop prognostic models. The area under the curve of the receiver-operator characteristic curve for prognostic prediction in the primary and validation KIRC cohorts was 0.84 and 0.82 at 2500 days of overall survival, respectively. In addition, splicing correlation networks revealed key splicing factors (SFs) in KIRC, such as HNRNPH1, HNRNPU, KHDBS1, KHDBS3, SRSF9, RBMX, SFQ, SRP54, HNRNPA0, and SRSF6. In this study, we analyzed the AS landscape in the TCGA KIRC cohort and detected predictors (prognostic) based on AS variants with high performance for risk stratification of the KIRC cohort and revealed key SFs in splicing networks, which could act as underlying mechanisms.
Subject(s)
Alternative Splicing/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Transcriptome , Computational Biology/methods , Databases, Genetic , Female , Follow-Up Studies , Gene Regulatory Networks , Humans , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , RNA-Seq , Risk Assessment , Risk Factors , Survival RateABSTRACT
Neuron-derived neurotrophic factor (NDNF) is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF has been identified as a neurotrophic factor; however, its role in carcinogenesis has not yet been identified. To investigate the expression and role of NDNF in carcinogenesis, the expression of NDNF in human Renal cell carcinoma (RCC) cell lines and tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell proliferation was investigated using CCK-8 and colony formation assays, and the cell invasion and immigration capacity was evaluated using the transwell assay. The results demonstrated that NDNF expression was downregulated in RCC cell lines and RCC tissues. Restoring NDNF expression significantly inhibited the proliferation, migration and invasion of RCC cells. The study also demonstrated that the inhibitory effect of NDNF on invasive ability was mediated by suppressing the epithelial-mesenchymal transition (EMT) in RCC cells. NDNF may therefore be considered an important regulator of EMT in RCC progression and may represent a novel promising target for antimetastatic therapy.
ABSTRACT
Nonobstructive azoospermia (NOA) or testicular failure is the most severe form of male infertility. A variety of conditions, both acquired and congenital, can cause azoospermia. However, in a large number of azoospermia patients who are classified as idiopathic cases, the etiology remains poorly understand mainly due to the lack of knowledge of all the genetic causes and molecular mechanisms responsible for spermatogenesis failure. Identification of the key gene modules and pathways-related spermatogenesis failure might help to reveal the mechanisms of idiopathic azoospermia. Therefore, the expression patterns of spermatogenesis-associated genes in NOA were analyzed by weighted gene coexpression network analysis (WGCNA) based on two public microarray data sets (GSE45885 and GSE45887), which included 51 samples and 32,321 genes. We identified a module (turquoise) that was significantly related to the Johnsen score of the testicular samples. In addition, the results of function and pathway enrichment analyses based on the online bioinformatics database Metascape revealed that genes in the turquoise module were mainly related to the process of spermatogenesis and spermatid development. To further identify spermatogenesis-associated genes, a microarray data set (GSE926) of murine testis at different developmental time points was analyzed by WGCNA. The blue module in GSE926 was significantly related to the time of murine testis development. The overlap study and k-core analysis based on protein-protein interaction network revealed that spermatogenesis- and spermatid development-associated genes, including glyceraldehyde-3-phosphate dehydrogenase, ADAM metallopeptidase domain 2, transition protein 1, testis-specific serine kinase 2, transition protein 2, and germ cell-associated 1 (GSG1), were further identified in the selected modules. The expression profile of GSG1 in human testis was chosen for further study using immunochemistry staining. Taken together, these screened gene modules and pathways provided a more detailed genetic and molecular mechanism underlying spermatogenesis failure occurrence and holds promise as potential diagnosis biomarkers and therapeutic targets.
Subject(s)
Azoospermia/genetics , Spermatogenesis/genetics , Testis/metabolism , Animals , Azoospermia/pathology , Chromosomal Proteins, Non-Histone/genetics , Computational Biology , Gene Expression Regulation, Developmental/genetics , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Humans , Male , Mice , Protein Interaction Maps/genetics , Protein Serine-Threonine Kinases/genetics , Testis/growth & development , Testis/pathologyABSTRACT
BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.
Subject(s)
Carcinoma, Renal Cell/physiopathology , Down-Regulation , Kidney Neoplasms/physiopathology , MicroRNAs/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , 3' Untranslated Regions , Animals , Antagomirs/metabolism , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Proto-Oncogene Proteins p21(ras)/metabolism , RNA Interference , RNA, Small Interfering/metabolism , RNA, Small Interfering/therapeutic use , Signal TransductionABSTRACT
Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a number of cancers and associated with poor prognosis. Here, we found that expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues and significantly associated with primary tumor stage and bladder cancer patients' poorer prognosis. Our data also showed decreased cell proliferation and migration rates of bladder cancer cell lines when the expression of KPNA2 and OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co-IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up-regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is correlated with increased aggressive tumor behavior. Also, we propose that KPNA2 regulates the process of OCT4 nuclear transportation in bladder cancer.
Subject(s)
Octamer Transcription Factor-3/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , alpha Karyopherins/genetics , Active Transport, Cell Nucleus , Adult , Aged , Apoptosis/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Gene Silencing , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Octamer Transcription Factor-3/genetics , Prognosis , RNA, Small Interfering/genetics , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
Wilms tumor or nephroblastoma is a common kidney malignant tumor in childhood, accounting for ~5% of all pediatric tumors. At present, reports on Wilms' tumor occurring in adults, particularly at ages >30 years, are extremely rare. The majority of the cases of adult Wilms' tumor are closely associated with chemotherapy. Furthermore, in rare cases, Wilms' tumor is characterized by three classic types of cells, namely blastemal, stromal and epithelial cells. We herein report a case of Wilms' tumor with three classic types of cells on histological examination in a 51 year-old male patient who had received prior chemotherapy. The patient promptly underwent radical nephrectomy and remains alive. A review of previously presented cases of adult Wilms' tumor from PubMed database was also performed.
ABSTRACT
Adrenal sarcomatoid carcinoma is a rare adrenal carcinoma. To the best of our knowledge, only 11 cases have been reported since 1987. Adrenal sarcomatoid carcinoma presents a diagnostic challenge due to its atypical symptoms and histological patterns. At the time of diagnosis, a large percentage of patients are already at the metastatic stage and succumb within a few months. The present study reports a case of a 59-year-old man presenting with asthenia and weight loss with adrenal sarcomatoid carcinoma metastatic to the lung. A computed tomography (CT) scan and ultrasonography of the patient's abdomen suggested a large homogeneous mass in the right adrenal gland, and a CT scan of his chest suggested lung metastasis. Right adrenalectomy was performed. Histological examination revealed that the tumor was composed of sarcomatous and carcinomatous differentiation elements. Immunohistochemical examination revealed tumor cell positivity for vimentin and cytokeratin. At the 6-month follow-up the patient exhibited no disease progression and refused further proposed treatment. The patient was alive at the time of writing the current report. The present case report additionally reviews the literature, for the purpose of raising awareness of these rare lesions and assisting in achieving accurate diagnoses and effective treatment.
ABSTRACT
C12orf59 is newly identified gene in kidney. However, the relation of C12orf59 expression and clinic features is unknown. Here, our study showed that C12orf59 was broadly expressed in normal human tissues with high expression levels in kidney while its expression is beyond detectable in a panel of cancer cell lines. C12orf59 expression in RCC was significantly decreased compared with corresponding adjacent noncancerous tissues (P < 0.01). The decreased C12orf59 expression was correlated with lymph node status (P < 0.05), distant metastases (P < 0.05), poor survival (P < 0.001) (HR 3.00; 95% CI, 1.29-7.53), VHL non-sense mutations or frame-shift mutations (P < 0.01), and UMPP gene non-sense mutations or frame-shift mutations (P = 0.01). Thus, we propose that the decreased C12orf59 expression status is a prognostic biomarker of ccRCC and cooperates with the loss of VHL all the while promoting renal carcinogenesis.
Subject(s)
Antigens, Neoplasm/genetics , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Membrane Proteins/genetics , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Antigens, Neoplasm/metabolism , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Down-Regulation , Female , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Male , Membrane Proteins/metabolism , Middle Aged , Mutation , Prognosis , Survival Rate , Von Hippel-Lindau Tumor Suppressor Protein/metabolismABSTRACT
Differential methylation of the homologous chromosomes, a well-known mechanism leading to genomic imprinting and X-chromosome inactivation, is widely reported at the non-imprinted regions on autosomes. To evaluate the transgenerational DNA methylation patterns in human, we analyzed the DNA methylomes of somatic and germ cells in a four-generation family. We found that allelic asymmetry of DNA methylation was pervasive at the non-imprinted loci and was likely regulated by cis-acting genetic variants. We also observed that the allelic methylation patterns for the vast majority of the cis-regulated loci were shared between the somatic and germ cells from the same individual. These results demonstrated the interaction between genetic and epigenetic variations and suggested the possibility of widespread sequence-dependent transmission of DNA methylation during spermatogenesis.
Subject(s)
Alleles , DNA Methylation , Epigenesis, Genetic , Family , Germ Cells/metabolism , Cluster Analysis , Computational Biology/methods , Genetic Loci , Genotype , High-Throughput Nucleotide Sequencing , Humans , Male , Molecular Sequence Annotation , Pedigree , Polymorphism, Single Nucleotide , Reproducibility of Results , Spermatozoa/metabolism , X Chromosome Inactivation/geneticsABSTRACT
MicroRNAs (miRNAs) are an important class of small, noncoding RNA molecules that regulate gene expression at the transcriptional or posttranscriptional level. They are involved in apoptosis, proliferation and migration and are known to have an important role in many types of cancer. Aberrant expression of miRNA451a (miR451a) has previously been reported in tumors, however its role in renal cell carcinoma (RCC) is currently unknown. The aim of the present study was to investigate the role of miR451a in RCC. The expression of miR451a was analyzed in 50 paired RCC and normal tissues by quantitative polymerase chain reaction. Furthermore, the effects of miR451a on cell migration, proliferation and apoptosis were evaluated, using migration scratch, MTT and flow cytometric assays. The present study demonstrated that miR451a was upregulated in RCC, as compared with paired normal tissues (P<0.05). Downregulation of miR451a using a synthesized inhibitor, significantly suppressed cell migration and proliferation, and induced apoptosis of renal cancer cells in vitro, as compared with a negative control (P<0.05). In the present study, it was determined that miR451a may have an important role as a tumor enhancer in RCC. These results imply that miR451a may be a promising therapeutic target for the treatment of RCC.
Subject(s)
Apoptosis/genetics , Carcinoma, Renal Cell/genetics , Cell Movement/genetics , Kidney Neoplasms/genetics , MicroRNAs/genetics , Adult , Aged , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Up-RegulationABSTRACT
BACKGROUND: Current knowledge about the molecular properties and prognostic markers of upper tract urothelial carcinoma (UTUC) is sparse and often based on bladder urothelial carcinoma (UC), which is thought to share common risk factors with UTUC. However, studies have suggested that differences exist regarding tumor behavior and molecular biology of these cancers, comprehensive investigations are needed to guide the clinical management of UTUC. In recent years, massively parallel sequencing has allowed insights into the biology of many cancers, and molecular prognostic markers based on this approach are rapidly emerging. The goal of this study was to characterize the gene expression patterns of UTUC using massively parallel sequencing, and identify potential molecular markers for prognosis in patients with UTUC. METHODS: We compared the genome-wide mRNA expression profile of cancer and matched normal tissues from 10 patients with UTUC to identify significantly deregulated genes. We also examined the protein levels of prognostic marker candidates in 103 patients with UTUC, and tested the association of these markers with overall survival using Kaplan-Meier model and Cox regression. RESULTS: Functional enrichment of significantly deregulated genes revealed that expression patterns of UTUC were characterized by disorders of cell proliferation and metabolism. And we also compared the expression profile of UTUC with that of bladder UC. Our results highlighted both shared (e.g. disorders of cell cycling and growth signal transduction) and tumor-specific (e.g. abnormal metabolism in UTUC and disruptions of adhesion pathways in bladder UC) features of these two cancers. Importantly, we identified that low protein expression of ALDH2 while high CCNE1 and SMAD3 were significantly associated with increased depth (*P <0.05) and lower overall survival (***P <0.0001) in an independent set of 103 patients. Multivariate Cox regression revealed that all these three genes were independent prognostic indicators in patients with UTUC (***P <0.001). CONCLUSIONS: In conclusion, our study characterized the comprehensive expression profile of UTUC and highlighted both commons and differences in expression patterns between UTUC and bladder UC. And we, for the first time, revealed that ALDH2, CCNE1 and SMAD3 are associated with prognosis in patients with UTUC.