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1.
Oncogene ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34997215

RESUMO

Cancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of POU domain class 2 transcription factor 1 (POU2F1) on metabolic reprogramming in colon cancer. The POU2F1 expression was analyzed in GEO dataset, TCGA cohorts and human colon cancer tissues by bioinformatics and immunohistochemistry. The effects of altered POU2F1 expression on proliferation, glucose metabolism and oxaliplatin sensitivity of colon cancer cells were tested. The impacts of POU2F1 on aldolase A (ALDOA) expression and malignant behaviors of colon cancer cells were examined. We found that up-regulated POU2F1 expression was associated with worse prognosis and oxaliplatin resistance in colon cancer. POU2F1 enhanced the proliferation, aerobic glycolysis and the pentose phosphate pathway (PPP) activity, but reduced oxidative stress and apoptosis in colon cancer cells, dependent on up-regulating ALDOA expression. Mechanistically, POU2F1 directly bound to the ALDOA promoter to enhance the ALDOA promoter activity in colon cancer cells. Moreover, activation of the POU2F1-ALDOA axis decreased the sensitivity to oxaliplatin in colon cancer cells. These data indicate that the POU2F1-ALDOA axis promotes the progression and oxaliplatin resistance by enhancing metabolic reprogramming in colon cancer. Our findings suggest that the POU2F1-ALDOA axis may be new therapeutic targets to overcome oxaliplatin resistance in colon cancer.

2.
J Cancer ; 13(1): 174-183, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976181

RESUMO

Lung cancer is the most common malignancy, being a serious threat of human lives. The incidence and mortality of lung cancer has been increasing rapidly in the past decades. Although the development of new therapeutic modes, such as target therapy, the overall survival rate of lung cancer remains low. It is urgent to advance the understanding of molecular oncology and find novel biomarkers and targets for the early diagnosis, treatment, and prognostic prediction of lung cancer. Long non-coding RNAs (lncRNAs) are non-protein coding RNA transcripts that are more than 200 nucleotides in length. LncRNAs exert diverse biological functions by regulating gene expressions at transcriptional, translational, and post-translational levels. In the past decade, it has been shown that lncRNAs are extensively involved in the pathogenesis of various diseases, including lung cancer. In this review, we highlighted the lncRNAs characterized in lung cancer and discussed their translational potential in lung cancer clinics.

3.
Sci Rep ; 11(1): 24367, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34934067

RESUMO

Persistent infection with high-risk types Human Papillomavirus could cause diseases including cervical cancers and oropharyngeal cancers. Nonetheless, so far there is no effective pharmacotherapy for treating the infection from high-risk HPV types, and hence it remains to be a severe threat to the health of female. Based on drug repositioning strategy, we trained and benchmarked multiple machine learning models so as to predict potential effective antiviral drugs for HPV infection in this work. Through optimizing models, measuring models' predictive performance using 182 pairs of antiviral-target interaction dataset which were all approved by the United States Food and Drug Administration, and benchmarking different models' predictive performance, we identified the optimized Support Vector Machine and K-Nearest Neighbor classifier with high precision score were the best two predictors (0.80 and 0.85 respectively) amongst classifiers of Support Vector Machine, Random forest, Adaboost, Naïve Bayes, K-Nearest Neighbors, and Logistic regression classifier. We applied these two predictors together and successfully predicted 57 pairs of antiviral-HPV protein interactions from 864 pairs of antiviral-HPV protein associations. Our work provided good drug candidates for anti-HPV drug discovery. So far as we know, we are the first one to conduct such HPV-oriented computational drug repositioning study.

4.
Comput Math Methods Med ; 2021: 2833043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917165

RESUMO

In this paper, a meta-analysis of the effectiveness and safety of intravenous thrombolysis in patients with acute cerebral infarction was carried out, the original literature inclusion criteria and retrieval strategies were developed, and the collection deadline was about new oral anticoagulants and other methods for the antithrombotic intravenous thrombolytic treatment of patients with acute cerebral infarction for the relevant literature on the safety and effectiveness comparison. First, the quality of the literature is evaluated according to whether the included studies are randomized controlled trials, whether there is randomized concealment, whether blinding is used, and whether they are withdrawn or lost to follow-up, and the RevMan 5.2 software is used for meta-analysis. At the same time, grey literature databases such as dissertations were experimentally searched, and all randomized controlled studies (RCT), nonrandomized controlled studies, case-controlled studies, cohort studies, case series reports, etc. of Wingspan in the treatment of intracranial atherosclerotic stenosis were collected. In the prevention of myocardial infarction in patients with acute cerebral infarction, the difference between the two was not statistically significant (RR = 0.82, 95% CI (0.57, 1.17), P = 0.27). Compared with other methods, it can significantly reduce the all-cause mortality of patients with nonvalvular venous thrombolysis, and the difference is statistically significant (RR = 0.90, 95% CI (0.85, 0.96), P = 0.001). Experimental results show that in terms of safety, the new oral anticoagulant is better than other methods in reducing minor bleeding in patients with acute cerebral infarction, and the difference is statistically significant (RR = 0.87, 95% CI (0.76, 0 99), P = 0.03); the effect is better than other methods in reducing the incidence of serious bleeding events, and the difference is statistically significant (RR = 0.79, 95% CI (0.74, 0.85), P < 0.00001).

5.
Genomics ; 114(1): 171-184, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34933069

RESUMO

Auxin response factors (ARFs) are transcription factors that regulate the transcription of auxin-responsive genes during plant growth and development. In this study, 29 and 30 ARF members were identified from the two wild peanut species, A. duranensis and A. ipaensis, respectively. The ARFs, including their classifications, conserved domains and evolutionary relationships were characterized. RNA-seq analyses revealed that some of the ARF genes were responsive to abiotic stress, particularly high salinity. In addition to abiotic stress, the expression of 2 ARF members was also regulated by biotic stress, specifically Bradyrhizobium infection in A. duranensis. The ARF gene Arahy.7DXUOK was predicted to be a potential target of miR160. Overexpression of miR160 could cause degradation of the Arahy.7DXUOK target gene transcript and increased salt tolerance in miR160OX transgenic plants. Therefore, these molecular characterization and expression profile analyses provide comprehensive information on ARF family members and will help to elucidate their functions to facilitate further research on peanuts.

6.
Mol Ther ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34793975

RESUMO

Alternative pre-mRNA splicing (AS) provides the potential to produce diversity at RNA and protein levels. Disruptions in the regulation of pre-mRNA splicing can lead to diseases. With the development of transcriptome and genome sequencing technology, increasing diseases have been identified to be associated with abnormal splicing of mRNAs. In tumors, abnormal alternative splicing frequently plays critical roles in cancer pathogenesis and may be considered as new biomarkers and therapeutic targets for cancer intervention. Metabolic abnormalities and immune disorders are important hallmarks of cancer. AS produces multiple different isoforms and diversifies protein expression, which is utilized by the immune and metabolic reprogramming systems to expand gene functions. The abnormal splicing events contributed to tumor progression, partially due to effects on immune response and metabolic reprogramming. Herein, we reviewed the vital role of alternative splicing in regulating cancer metabolism and immune response. We discussed how alternative splicing regulates metabolic reprogramming of cancer cells and antitumor immune response, and the possible strategies to targeting alternative splicing pathways or splicing-regulated metabolic pathway in the context of anticancer immunotherapy. Further, we highlighted the challenges and discuss the perspectives for RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms.

7.
Br J Cancer ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750493

RESUMO

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.

8.
Plant Physiol Biochem ; 168: 167-176, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34634642

RESUMO

Abiotic stressors, such as drought and high salinity, seriously affect plant growth, productivity, and quality. Maintaining reactive oxygen species (ROS) homeostasis and osmotic balance plays a crucial role in abiotic stress tolerance. ß-amylase (BAM) hydrolyzes α-1,4-glycosidic bonds by releasing maltose from starch in the regulation of soluble sugars. However, the function and mechanism of BAMs related to abiotic stress resistance remain unclear in sweetpotato (Ipomoea batatas (L.) Lam.). In this study, we isolated a novel ß-amylase gene IbBAM1.1, which was strongly induced by PEG6000, NaCl, and maltose treatments in sweetpotato variety Yanshu25. Overexpression of IbBAM1.1 conferred enhanced tolerance to the drought and high salinity stressors in Arabidopsis thaliana. The activity of ß-amylase and the degradation of starch were promoted under drought or salt stress. Accordingly, the contents of osmoprotectants, including maltose and proline were significantly higher in the transgenic lines than those in wild type (WT) plants. Less ROS, such as H2O2 and O2-, accumulated in the overexpressing lines than in WT plants. Superoxide dismutase activity was strongly enhanced and the level of malondialdehyde was lower under the drought or salt treatment in transgenic plants. Taken together, these results demonstrate that IbBAM1.1 acted as a positive regulator, at least in part, by regulating the level of osmoprotectants to balance the osmotic pressure and activate the scavenging system to maintain ROS homeostasis in the plants.

9.
Theor Appl Genet ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647130

RESUMO

KEY MESSAGE: Six major QTLs for wheat grain size and weight were identified on chromosomes 4A, 4B, 5A and 6A across multiple environments, and were validated in different genetic backgrounds. Grain size and weight are crucial components of wheat yield. Dissection of their genetic control is thus essential for the improvement of yield potential in wheat breeding. We used a doubled haploid (DH) population to detect quantitative trait loci (QTLs) for grain width (GW), grain length (GL), and thousand grain weight (TGW) in five environments. Six major QTLs, QGw.cib-4B.2, QGl.cib-4A, QGl.cib-5A.1, QGl.cib-6A, QTgw.cib-4B, and QTgw.cib-5A, were consistently identified in at least three individual environments and in best linear unbiased prediction (BLUP) datasets, and explained 5.65-34.06% of phenotypic variation. QGw.cib-4B.2, QTgw.cib-4B, QGl.cib-5A.1 and QGl.cib-6A had no effect on grain number per spike (GNS). In addition to QGl.cib-4A, the other major QTLs were further validated by using Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. Moreover, significant interactions between the three major GL QTLs and two major TGW QTLs were observed. Comparison analysis showed that QGl.cib-5A.1 and QGl.cib-6A are likely new loci. Notably, QGw.cib-4B.2 and QTgw.cib-4B were co-located on chromosome 4B and improved TGW by increasing only GW, unlike nearby or overlapped loci reported previously. Three genes associated with grain development within the QGw.cib-4B.2/QTgw.cib-4B interval were identified by searches on sequence similarity, spatial expression patterns, and orthologs. The major QTLs and KASP markers reported here will be useful for elucidating the genetic architecture of grain size and weight and for developing new wheat cultivars with high and stable yield.

10.
J Cell Physiol ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34676546

RESUMO

Circular RNAs (circRNAs) are closed back-splicing products of precursor mRNA in eukaryotes. Compared with linear mRNAs, circRNAs have a special structure and stable expression. A large number of studies have provided different regulatory mechanisms of circRNAs in tumors. Challenges exist in understanding the control of circRNAs because of their sequence overlap with linear mRNA. Here, we survey the most recent progress regarding the regulation of circRNA biogenesis by RNA-binding proteins, one of the vital functional proteins. Furthermore, substantial circRNAs exert compelling biological roles by acting as protein sponges, by being translated themselves or regulating posttranslational modifications of proteins. This review will help further explore more types of functional proteins that interact with circRNA in cancer and reveal other unknown mechanisms of circRNA regulation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34714119

RESUMO

AIMS: Rhodiola sacra is a widely-used pharmaceutical component with multiple functions, including anti-oxidation and anti-inflammation. However, the exact mechanisms involved in neuroprotection against transient global cerebral ischemia (tGCI) remains to be elucidated. Herein we aim to close the gap in understanding on whether rhodiola sacra reduces neuronal death in hippocampal CA1 and demonstrate how rhodiola sacra offers neuroprotection after tGCI. RESULTS: The results show that rhodiola sacra (2.4 g/kg/d by feeding) pretreatment or/and postreatment significantly alleviated neuronal injury, inhibited glial activation and improved cognitive function in male rats subjected to tGCI. The neuroprotection of prophylaxis with rhodiola sacra is equivalent to that of therapeutics. The binding mode of adenosine monophosphate-activated protein kinase (AMPK) α2-subunit with rhodiola sacra was predicted by molecular docking. Furthermore, rhodiola sacra upregulates phosphorylated AMPK and promotes nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2). Additionally, rhodiola sacra increases heme oxygenase-1 (HO-1) expression and activity and reduces malondialdehyde (MDA) content in CA1 after tGCI. However, the neuroprotection of rhodiola sacra is abolished by Nrf2 knockdown with small interfering RNA (siRNA) after tGCI. Similarly, the inhibition of AMPK with Compound C or siRNA against AMPK α2 aggravates neuronal death after tGCI through decreasing nuclear Nrf2 and the expression and activity of HO-1, and increasing the release of MDA. Innovation and Conclusion: For the first time this study demonstrates that as a prophylactic or therapeutic agent rhodiola sacra prevents oxidant stress, protects neurons and improves cognitive function through activating the AMPK/Nrf2 pathway in tGCI rats.

12.
Int J Gen Med ; 14: 5397-5404, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526808

RESUMO

Purpose: Venous thromboembolism (VTE) is a common complication of intracerebral hemorrhage (ICH) patients in intensive care unit (ICU), but anticoagulation therapy of ICH patients with VTE remains controversial. We aim to explore the risk factors and prognosis of anticoagulation therapy in ICH patients with VTE. Patients and Methods: Medical records of ICH patients were collected from the Medical Information Mart for Intensive Care III (MIMIC-III version 1.4) database. The risk factors and prognosis of anticoagulation therapy in ICH patients with VTE were assessed by multivariable logistic regression analysis and Kaplan-Meier survival analysis, respectively. Results: A total of 848 ICH patients were included in our study, of whom 69 ICH patients with VTE were screened, including 58 patients with deep vein thrombosis (DVT), 12 patients with pulmonary embolism (PE), and 1 patient with DVT and PE. In the multivariable logistic regression analysis, malignancy (odds ratio (OR): 4.262, 95% confidence interval (CI): 2.263-8.027, P=0.000), pulmonary circulation disease (OR: 28.717, 95% CI: 9.566-86.208, P=0.000), coagulopathy (OR: 2.453, 95% CI: 1.098-5.483, P=0.029), age > 60 years old (OR: 2.138, 95% CI: 1.087-4.207, P=0.028) and hospitalization time > 16 days (OR: 2.548, 95% CI: 1.381-4.701, P=0.003) were independent risk factors for VTE in ICH patients. Kaplan-Meier survival analysis and log-rank test found that, compared to non-anticoagulation group, anticoagulation group had higher cumulative survival rates during hospitalization, 28-day, 3-month, 1-year, and 4-year after admission, respectively. Conclusion: Malignancy, pulmonary circulation disease, coagulopathy, age >60 years old and hospitalization time >16 days were independent risk factors for VTE in ICH patients, and anticoagulation therapy for VTE in ICH patients may be safe and effective. These findings need to be verified by more high-quality and well-designed randomized controlled trials.

13.
Front Pharmacol ; 12: 724416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305622

RESUMO

[This corrects the article DOI: 10.3389/fphar.2020.599577.].

14.
Theor Appl Genet ; 134(11): 3625-3641, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34309684

RESUMO

KEY MESSAGE: Two major and stable QTLs for spike compactness and length were detected and validated in multiple genetic backgrounds and environments, and their pleiotropic effects on yield-related traits were analyzed. Spike compactness (SC) and length (SL) are greatly associated with wheat (Triticum aestivum L.) grain yield. To detect quantitative trait loci (QTL) associated with SC and SL, two biparental populations derived from crosses of Chuanmai42/Kechengmai1 and Chuanmai42/Chuannong16 were employed to perform QTL mapping in five environments. A total of 34 QTLs were identified, in which six major QTLs were repeatedly detected in more than four environments and the best linear unbiased prediction datasets, explaining 7.13-33.6% of phenotypic variation. These major QTLs were co-located in two genomic regions on chromosome 5A and 6A, namely QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. By developing kompetitive allele-specific PCR (KASP) markers that linked to them, the two loci were validated in different genetic backgrounds, and their interactions were also analyzed. Comparison analysis showed that QSc/Sl.cib-5A was not Vrn-A1 and Q, and QSc/Sl.cib-6A was likely a new locus for SC and SL. Both QSc/Sl.cib-5A and QSc/Sl.cib-6A had pleiotropic effects on other yield-related traits including plant height, thousand grain weight and grain length. Therefore, the two loci combined with the developed KASP markers might be potentially applicable in wheat breeding. Furthermore, based on the spatiotemporal expression patterns, gene annotation, orthologous search and sequence differences, TraesCS5A01G301400 and TraesCS6A01G090300 were considered as potential candidates for QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. These results provided valuable information for fine mapping and cloning of the two loci in the future.


Assuntos
Locos de Características Quantitativas , Sementes/crescimento & desenvolvimento , Triticum/genética , Alelos , Mapeamento Cromossômico , Patrimônio Genético , Ligação Genética , Marcadores Genéticos , Pleiotropia Genética , Fenótipo
15.
Theor Appl Genet ; 134(10): 3225-3236, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34132847

RESUMO

KEY MESSAGE: Decisive role of reduced vrs1 transcript abundance in six-rowed spike of barley carrying vrs1.a4 was genetically proved and its potential causes were preliminarily analyzed. Six-rowed spike 1 (vrs1) is the major determinant of the six-rowed spike phenotype of barley (Hordeum vulgare L.). Alleles of Vrs1 have been extensively investigated. Allele vrs1.a4 in six-rowed barley is unique in that it has the same coding sequence as Vrs1.b4 in two-rowed barley. The determinant of row-type in vrs1.a4 carriers has not been experimentally identified. Here, we identified Vrs1.b4 in two-rowed accessions and vrs1.a4 in six-rowed accessions from the Qinghai-Tibet Plateau at high frequency. Genetic analyses revealed a single nuclear gene accounting for row-type alteration in these accessions. Physical mapping identified a 0.08-cM (~ 554-kb) target interval on chromosome 2H, wherein Vrs1 was the most likely candidate gene. Further analysis of Vrs1 expression in offspring of the mapping populations or different Vrs1.b4 and vrs1.a4 lines confirmed that downregulated expression of vrs1.a4 causes six-rowed spike. Regulatory sequence analysis found a single 'TA' dinucleotide deletion in vrs1.a4 carriers within a 'TA' tandem-repeat-enriched region ~ 1 kb upstream of the coding region. DNA methylation levels did not correspond to the expression difference and therefore did not affect Vrs1 expression. More evidence is needed to verify the causal link between the 'TA' deletion and the downregulated Vrs1 expression and hence the six-rowed spike phenotype.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Regulação da Expressão Gênica de Plantas , Hordeum/crescimento & desenvolvimento , Hordeum/genética , Fenótipo , Proteínas de Plantas/metabolismo , Metilação de DNA , Filogenia , Proteínas de Plantas/genética
16.
World J Surg Oncol ; 19(1): 181, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154624

RESUMO

PURPOSE: We aimed to develop and validate a radiomics model for differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH) in non-cirrhotic livers using Gd-DTPA contrast-enhanced magnetic resonance imaging (MRI). METHODS: We retrospectively enrolled 149 HCC and 75 FNH patients treated between May 2015 and May 2019 at our center. Patients were randomly allocated to a training (n=156) and validation set (n=68). In total, 2260 radiomics features were extracted from the arterial phase and portal venous phase of Gd-DTPA contrast-enhanced MRI. Using Max-Relevance and Min-Redundancy, random forest, least absolute shrinkage, and selection operator algorithm for dimensionality reduction, multivariable logistic regression was used to build the radiomics model. A clinical model and combined model were also established. The diagnostic performance of the models was compared. RESULTS: Eight radiomics features were chosen for the radiomics model, and four clinical factors (age, sex, HbsAg, and enhancement pattern) were chosen for the clinical model. A combined model was built using the factors from the previous models. The classification accuracy of the combined model differentiated HCC from FNH in both the training and validation sets (0.956 and 0.941, respectively). The area under the receiver operating characteristic curve of the combined model was significantly better than that of the clinical model for both the training (0.984 vs. 0.937, p=0.002) and validation (0.972 vs. 0.903, p=0.032) sets. CONCLUSIONS: The combined model provided a non-invasive quantitative method for differentiating HCC from FNH in non-cirrhotic liver with high accuracy. Our model may assist clinicians in the clinical decision-making process.


Assuntos
Carcinoma Hepatocelular , Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Hiperplasia Nodular Focal do Fígado/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Prognóstico , Estudos Retrospectivos
17.
Front Oncol ; 11: 674426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079763

RESUMO

RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

18.
Signal Transduct Target Ther ; 6(1): 240, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34168109

RESUMO

Actin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients' poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients' early diagnosis and therapy.

19.
Cytometry A ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34173319

RESUMO

Human basophils are terminally differentiated granulocytes that are least abundant in the peripheral blood but play important roles in allergic diseases. Studies on human basophils are limited by the high cost on the isolation of human basophils by magnetic-activated cell sorting (MACS) for negative depletion of non-basophils, followed by CD123-based positive selection of basophils. Moreover, such CD123-based purification of basophils may be limited by blocking of the binding of IL-3/anti-CD123 to the surface CD123. Here we identified SSClow CD4- CD127- HLA-DR- CRTH2high as unique markers for the identification of human basophils through stringent flow cytometric analysis of leukocytes from buffy coat. We established an efficient and cost-effective method for isolating human basophils from buffy coat based on positive magnetic selection of CRTH2+ cells followed by flow cytometric sorting of SSClow CD4- CD127- HLA-DR- CRTH2high cells. Approximately 1 to 1.5 million basophils were isolated from one buffy coat with a purity of >97%. Basophils purified by this method were viable and efficiently responded to key regulators of basophils including IL-3 and anti-IgE. This method can be used for purifying human basophils for subsequent functional studies.

20.
Theor Appl Genet ; 134(8): 2481-2494, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33942136

RESUMO

KEY MESSAGE: A novel qualitative locus regulating the uppermost internode elongation of barley was identified and mapped on 6H, and the candidate gene mining was performed by employing various barley genomic resources. The stem of grass crops, such as barley and wheat, is composed of several interconnected internodes. The extent of elongation of these internodes determines stem height, and hence lodging, canopy architecture, and grain yield. The uppermost internode (UI) is the last internode to elongate. Its elongation contributes largely to stem height and facilitates spike exsertion, which is crucial for final grain yield. Despite the molecular mechanism underlying regulation of UI elongation was extensively investigated in rice, little is known in barley. In this study, we characterized a barley spontaneous mutant, Sheathed Spike 1 (SS1), showing significantly shortened UI and sheathed spike (SS). The extension of UI parenchyma cell in SS1 was significantly suppressed. Exogenous hormone treatments and RNA-seq analysis indicated that the suppression of UI elongation is possibly related to insufficient content of endogenous bioactive gibberellin. Genetic analysis showed that SS1 is possibly controlled by a qualitative dominant nuclear factor. Bulked segregant analysis and further molecular marker mapping identified a novel major locus, HvSS1, in a recombination cold spot expanding 173.44-396.33 Mb on chromosome 6H. The candidate gene mining was further conducted by analyzing sequence differences, spatiotemporal expression patterns, and variant distributions of genes in the candidate interval by employing various barley genomic resources of worldwide collections of barley accessions. This study made insight into genetic control of UI elongation in barley and laid a solid foundation for further gene cloning and functional characterization. The results obtained here also provided valuable information for similar research in wheat.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Regulação da Expressão Gênica de Plantas , Hordeum/crescimento & desenvolvimento , Hordeum/genética , Fenótipo , Proteínas de Plantas/metabolismo , Clonagem Molecular , Proteínas de Plantas/genética
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