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1.
Mol Cell ; 83(24): 4494-4508.e6, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38016476

RESUMEN

In the cytoplasm, mRNAs are dynamically partitioned into translating and non-translating pools, but the mechanism for this regulation has largely remained elusive. Here, we report that m6A regulates mRNA partitioning between polysome and P-body where a pool of non-translating mRNAs resides. By quantifying the m6A level of polysomal and cytoplasmic mRNAs with m6A-LAIC-seq and m6A-LC-MS/MS in HeLa cells, we observed that polysome-associated mRNAs are hypo-m6A-methylated, whereas those enriched in P-body are hyper-m6A-methylated. Downregulation of the m6A writer METTL14 enhances translation by switching originally hyper-m6A-modified mRNAs from P-body to polysome. Conversely, by proteomic analysis, we identify a specific m6A reader IGF2BP3 enriched in P-body, and via knockdown and molecular tethering assays, we demonstrate that IGF2BP3 is both necessary and sufficient to switch target mRNAs from polysome to P-body. These findings suggest a model for the dynamic regulation of mRNA partitioning between the translating and non-translating pools in an m6A-dependent manner.


Asunto(s)
Adenina , Cuerpos de Procesamiento , Biosíntesis de Proteínas , Proteínas de Unión al ARN , Humanos , Cromatografía Liquida , Células HeLa , Polirribosomas/genética , Proteómica , ARN Mensajero/genética , Espectrometría de Masas en Tándem , Adenina/análogos & derivados , Adenina/metabolismo , Proteínas de Unión al ARN/metabolismo
2.
Respir Res ; 25(1): 18, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178073

RESUMEN

OBJECTIVE: We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. METHODS: Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. RESULTS: Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. CONCLUSIONS: The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Variaciones en el Número de Copia de ADN , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Bases de Datos Factuales , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Medición de Riesgo , Pronóstico
3.
Nucleic Acids Res ; 50(D1): D817-D827, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34718748

RESUMEN

Virus infections are huge threats to living organisms and cause many diseases, such as COVID-19 caused by SARS-CoV-2, which has led to millions of deaths. To develop effective strategies to control viral infection, we need to understand its molecular events in host cells. Virus related functional genomic datasets are growing rapidly, however, an integrative platform for systematically investigating host responses to viruses is missing. Here, we developed a user-friendly multi-omics portal of viral infection named as MVIP (https://mvip.whu.edu.cn/). We manually collected available high-throughput sequencing data under viral infection, and unified their detailed metadata including virus, host species, infection time, assay, and target, etc. We processed multi-layered omics data of more than 4900 viral infected samples from 77 viruses and 33 host species with standard pipelines, including RNA-seq, ChIP-seq, and CLIP-seq, etc. In addition, we integrated these genome-wide signals into customized genome browsers, and developed multiple dynamic charts to exhibit the information, such as time-course dynamic and differential gene expression profiles, alternative splicing changes and enriched GO/KEGG terms. Furthermore, we implemented several tools for efficiently mining the virus-host interactions by virus, host and genes. MVIP would help users to retrieve large-scale functional information and promote the understanding of virus-host interactions.


Asunto(s)
Bases de Datos Factuales , Interacciones Microbiota-Huesped , Virosis , Animales , Secuenciación de Inmunoprecipitación de Cromatina , Ontología de Genes , Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Microbiota-Huesped/genética , Humanos , Metadatos , Análisis de Secuencia de ARN , Programas Informáticos , Transcriptoma , Interfaz Usuario-Computador , Virosis/genética , Virosis/metabolismo , Navegador Web
4.
Angew Chem Int Ed Engl ; 60(2): 910-916, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-32939926

RESUMEN

Current plasmonic photocatalysts are mainly based on noble metal nanoparticles and rarely work in the infrared (IR) light range. Herein, cost-effective Bi2 O3-x with oxygen vacancies was formed in situ on commercial bismuth powder by calcination at 453.15 K in atmosphere. Interestingly, defects introduced into Bi2 O3-x simultaneously induced a localized surface plasmon resonance (LSPR) in the wavelength range of 600-1400 nm and enhanced the adsorption for CO2 molecules, which enabled efficient photocatalysis of CO2 -to-CO (ca. 100 % selectivity) even under low-intensity near-IR light irradiation. Significantly, the apparent quantum yield for CO evolution at 940 nm reached 0.113 %, which is approximately 4 times that found at 450 nm. We also showed that the unique LSPR allows for the realization of a nearly linear dependence of photocatalytic CO production rate on light intensity and operating temperature. Finally, based on an IR spectroscopy study, an oxygen-vacancy induced Mars-van Krevlen mechanism was proposed to understand the CO2 reduction reactions.

5.
Cancer Sci ; 109(4): 1012-1023, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29397041

RESUMEN

The cell cycle-related and expression-elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non-small-cell lung cancer (NSCLC) remains unclear. In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western blot analysis, and RT-PCR. The correlation between CREPT expression and clinicopathologic features was analyzed in 271 NSCLC patients. The prognostic value of CREPT expression was evaluated by Kaplan-Meier analysis and Cox regression analysis. CREPT was overexpressed in Calu-1 cell lines by using plasmid vector and its biological function was explored both in vitro and in vivo. We found that CREPT was significantly overexpressed in NSCLC compared with paired adjacent non-tumor tissues, and the expression level of CREPT was correlated with tumor differentiation, lymph node metastasis, and clinical stage. Kaplan-Meier analysis showed that the recurrence-free survival and overall survival of high CREPT expression groups were significantly shorter than those of the low CREPT expression group. Multivariate analysis identified that CREPT might be an independent biomarker for the prediction of NSCLC prognosis. Overexpression of CREPT increased cell proliferation and enhanced the migration and invasion ability of Calu-1 cells (a human NSCLC cell line with relative low CRPET expression) in vitro. Moreover, CREPT overexpression promoted tumor growth in a nude mice model. These results suggest that CREPT is closely relevant to the proliferation of NSCLC cells and it might be a potential prognostic marker in NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/metabolismo , Células A549 , Animales , Biomarcadores de Tumor/metabolismo , Diferenciación Celular/fisiología , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico
6.
Analyst ; 139(2): 455-63, 2014 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-24303521

RESUMEN

Somatic mutations in the epidermal growth factor receptor (EGFR) gene were associated with sensitivity to small molecule tyrosine kinase inhibitors for patients with lung adenocarcinomas. In this research, EGFR mutation status was analyzed by DNA sequencing in 153 lung adenocarcinoma tissues. Of these, 75 samples carried EGFR mutations, including 29 with E19del mutation, 33 with L858R mutation, 7 with T790M mutation, and 6 with multiple mutations. Then, 30 samples including 10 with wild type (wt)-EGFR, 10 with L858R and 10 with E19del mutations were selected for Raman and immunohistochemistry (IHC) analyses. After removing the spectra from normal and non-mutated regions, 441 spectra were found appropriate for Raman analysis: 149 from wt-EGFR, 135 from L858R and 157 from E19del mutations. The Raman peaks at 675, 1107, 1127 and 1582 cm(-1) were significantly increased in wt-EGFR tissues which can be attributed to specific amino acids and DNA. The Raman peaks at 1085, 1175 and 1632 cm(-1) assigned to arginine were slightly increased in L858R tissues. The overall intensity of E19del tissues was weaker than others due to exon 19 deletion that removes residues 746-750 of the expressed protein. Principal component analysis (PCA) and support vector machine (SVM) were applied for final prediction. The PCA/SVM algorithm yielded an overall accuracy of 87.8% for diagnosing L858R or E19del from wt-EGFR tissues. Finally, RS provides a simple, rapid and low-cost procedure based upon the molecular signatures for predicting EGFR mutation status.


Asunto(s)
Adenocarcinoma/genética , Análisis Mutacional de ADN/métodos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Espectrometría Raman/métodos , Adenocarcinoma del Pulmón , Algoritmos , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Máquina de Vectores de Soporte
7.
Commun Biol ; 7(1): 694, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844830

RESUMEN

Wounding initiates intricate responses crucial for tissue repair and regeneration. Yet, the gene regulatory networks governing wound healing remain poorly understood. Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C. elegans: response, repair, and remodeling. Integrating diverse datasets, we constructed a dynamic regulatory network comprising 241 transcription regulators and their inferred targets. We identified potentially seven autoregulatory TFs and five cross-autoregulatory loops involving pqm-1 and jun-1. We revealed that TFs might interact with chromatin factors and form TF-TF combinatory modules via intrinsically disordered regions to enhance response robustness. We experimentally validated six regulators functioning in transcriptional and translocation-dependent manners. Notably, nhr-76, daf-16, nhr-84, and oef-1 are potentially required for efficient repair, while elt-2 may act as an inhibitor. These findings elucidate transcriptional responses and hierarchical regulatory networks during C. elegans wound repair, shedding light on mechanisms underlying tissue repair and regeneration.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Redes Reguladoras de Genes , Cicatrización de Heridas , Animales , Caenorhabditis elegans/genética , Cicatrización de Heridas/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Análisis de Secuencia de ARN , Regulación de la Expresión Génica
8.
Chem Commun (Camb) ; 60(75): 10390-10393, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39224044

RESUMEN

A new Ru-catalyzed C-H activation/cyclization reaction for the synthesis of 3-C-glycosyl isocoumarins and 2-glycosyl-4H-chromen-4-ones with carbonyl sulfoxonium ylide glycogen are reported. In this catalytic system, benzoic acid and its derivatives react with carbonyl sulfoxonium ylide glycogen to yield isocoumarin C-glycosides, while 2-hydroxybenzaldehyde substrates react to produce chromone C-glycosides. These reactions were characterized by mild reaction conditions, broad substrate scope, high functional-group compatibility, and high stereoselectivity to yield several high-value isocoumarins and chromone skeleton-containing C-glycosides. The methods were successfully implemented in the context of large-scale reactions and the late-stage modification of complex natural products.

9.
Org Lett ; 26(24): 5092-5097, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38848493

RESUMEN

New carbonyl sulfoxonium ylide glyco-reagents have been developed, enabling the synthesis of versatile heteroarene C-glycosides through a Ru-catalyzed C-H activation/annulation strategy. These reactions tolerate various saccharide donors and represent a significant advance in the stereoselective synthesis of heterocyclic C-glycosides. Furthermore, the strategy and methods could be applied to large-scale reactions and late-stage modifications of some structurally complex natural products or drugs.

10.
Chem Commun (Camb) ; 60(5): 598-601, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38099839

RESUMEN

A new Cp*Rh(III)-catalyzed regioselective cyclization reaction of aromatic amides with allenes is reported. The use of allenyl derivatives bearing a directing-group assistant as a reaction promoter was the key to the success of this protocol. In this catalytic system, N-(pivaloyloxy)benzamide substrates react with allenes via Rh-σ-alkenyl intermediates, while N-(pivaloyloxy) indol substrates react via Rh-π-allyl intermediates. These reactions were characterized by mild reaction conditions, a broad substrate scope, and high functional-group compatibility to yield several high-value isoquinolinone and pyrimido[1,6-a]indol-1(2H)-one skeleton-containing compounds. The synthetic applications and primary mechanisms were also investigated.

11.
Front Immunol ; 14: 1091165, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36817461

RESUMEN

Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management.


Asunto(s)
Neoplasias Pulmonares , Microbiota , Humanos , Pulmón , Microbiota/fisiología
12.
Cancer Med ; 12(5): 5545-5557, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36325966

RESUMEN

OBJECTIVE: Mutations in driver genes contribute to the development and progression of lung adenocarcinoma (LUAD). However, in the dynamic evolutionary process from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and eventually to invasive adenocarcinoma (IAC), the role of driver genes is currently unclear. This study aimed to analyse the role of driver gene status in the progression of LUAD from preneoplasia to IAC. METHODS: Patients with LUAD who underwent surgery in our centre from March 2015 to December 2019 were retrospectively analysed, and LUAD patients with tumour sizes ≤3.0 cm and pN0 were included in the final analysis. The mutation status of common driver genes, including EGFR, ALK and ROS1, was detected. According to the pathological characteristics, the patients were divided into three stages: AIS, MIA and IAC. We analysed the distribution of driver gene mutation frequencies across three stages of LUAD. In addition, we performed univariate and multivariate analyses of IAC patients to screen for relevant variables (driver genes and clinicopathological features) affecting their prognosis. RESULTS: Ultimately, 759 patients with LUAD were enrolled, including 135, 130, and 494 cases of AIS, MIA, and IAC, respectively. EGFR mutations were identified in 359 (61.8%) patients, and with the transition from AIS to MIA, the frequency of EGFR mutations increased from 33.3% to 50.8%, p = 0.004, whereas the frequency of EGFR mutations was comparable for MIA and IAC (50.8% vs. 50.2%, p = 0.922). Moreover, ALK and ROS1 gene fusions were identified in 17 cases (2.2%) and 2 cases (3.0‰) respectively. For AIS, neither ALK gene nor ROS1 gene fusions were observed. When the tumour progressed to MIA, the ALK fusion frequency was 2.3% (3/130), which was basically consistent with the ALK fusion frequency of 2.8% in IAC, p = 0.143. For IAC, fusions of ROS1 fell into this category. In addition, we found that 40 patients (5.3%) developed metastasis/recurrence, and 14 patients (1.8%) died of cancer-specific related diseases. Notably, for AIS, there were no recurrences and no deaths, and for MIA, only 1 patient died with LUAD. Finally, survival analysis was performed in patients with stage IA invasive adenocarcinoma, and EGFR-mutant patients showed better DFS than EGFR-wild-type patients (p = 0.036). Conversely, patients with ALK fusions showed worse DFS than those with ALK wild-type (p = 0.004), and the same results were found in OS analysis. CONCLUSIONS: The accumulation of EGFR driver gene mutation frequencies mediates the progression of LUAD from AIS to MIA. When the tumour progresses to stage IA invasive adenocarcinoma, multivariate analysis based on driver gene status can be used as a pivotal prognostic factor.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Proteínas Tirosina Quinasas/genética , Estudios Retrospectivos , Proteínas Proto-Oncogénicas/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma/patología , Proteínas Tirosina Quinasas Receptoras/genética , Receptores ErbB/genética , Mutación
13.
Front Immunol ; 14: 1095388, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969176

RESUMEN

The development and growth of tumors remains an important and ongoing threat to human life around the world. While advanced therapeutic strategies such as immune checkpoint therapy and CAR-T have achieved astonishing progress in the treatment of both solid and hematological malignancies, the malignant initiation and progression of cancer remains a controversial issue, and further research is urgently required. The experimental animal model not only has great advantages in simulating the occurrence, development, and malignant transformation mechanisms of tumors, but also can be used to evaluate the therapeutic effects of a diverse array of clinical interventions, gradually becoming an indispensable method for cancer research. In this paper, we have reviewed recent research progress in relation to mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, to help guide the future study of malignant mechanisms and tumor prevention.


Asunto(s)
Neoplasias Hematológicas , Neoplasias , Humanos , Animales , Ratones , Ratas , Neoplasias/genética , Neoplasias/terapia , Inmunoterapia Adoptiva/métodos , Modelos Animales de Enfermedad , Animales Modificados Genéticamente
14.
Genome Biol ; 24(1): 49, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36918913

RESUMEN

BACKGROUND: The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood. RESULTS: Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless (fl) cotton (Gossypium hirsutum). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by the trans factors GhTCP14s to modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells. CONCLUSIONS: We uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.


Asunto(s)
Fibra de Algodón , Gossypium , Perfilación de la Expresión Génica , Fenotipo , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
15.
Cancers (Basel) ; 14(22)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36428703

RESUMEN

BACKGROUND: Esophageal cancer is still a leading cause of death among all tumors in males, with unsatisfactory responses to novel immunotherapies such as anti-PD-1 agents. Herein, we explored the role of CD155 in esophageal squamous cell cancer (ESCA) and its underlying molecular mechanisms. METHODS: Publicly available datasets were used for differential gene expression and immune infiltration analyses, and their correlation with patient survival. A total of 322 ESCA and 161 paracancer samples were collected and evaluated by performing immunohistochemistry and the H score was obtained by performing semiquantitative analysis. In vitro transfection of ESCA cell lines with lentivirus vectors targeting CD155 was performed to knockdown the protein. These cells were analyzed by conducting RNA sequencing, and the effects of CD155 knockdown on cell cycle and apoptosis were verified with flow cytometry and Western blotting. In addition, in vivo experiments using these engineered cell lines were performed to determine the role of CD155 in tumor formation. A small interfering RNA-mediated knockdown of Nectin3 was used to determine whether it phenocopied the profile of CD155 knockdown. RESULTS: CD155 is highly expressed in ESCA tissues and is positively associated with PD1, PDL1, CD4, IL2RA, and S100A9 expression. Furthermore, CD155 knockdown inhibited ESCA cells' proliferation by impairing the cell cycle and inducing cell apoptosis. Bioinformatics analysis of the gene expression profile of these engineered cells showed that CD155 mainly contributed to the regulation of PI3K/Akt and MAPK signals. The downregulation of Nectin3 expression phenocopied the profile of CD155 knockdown. DISCUSSION: CD155 may cooperate with PD-1/PD-L1 to support ESCA proliferation in ways other than regulating its underlying immune mechanisms. Indeed, CD155 downregulation can impair ESCA cell pro-cancerous behavior via the inhibition of the PI3K/Akt and MAPK signaling pathways. Moreover, Nectin3 may be a ligand of CD155 and participate in the regulation of ESCA cells' proliferation. Hence, the inhibition of CD155 may enhance the therapeutic effect of anti-PD-1 immunotherapies in ESCA.

16.
Nat Struct Mol Biol ; 29(1): 21-31, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35013598

RESUMEN

Analogous to alternative splicing, alternative polyadenylation (APA) has long been thought to occur independently at proximal and distal polyA sites. Using fractionation-seq, we unexpectedly identified several hundred APA genes in human cells whose distal polyA isoforms are retained in chromatin/nuclear matrix and whose proximal polyA isoforms are released into the cytoplasm. Global metabolic PAS-seq and Nanopore long-read RNA-sequencing provide further evidence that the strong distal polyA sites are processed first and the resulting transcripts are subsequently anchored in chromatin/nuclear matrix to serve as precursors for further processing at proximal polyA sites. Inserting an autocleavable ribozyme between the proximal and distal polyA sites, coupled with a Cleave-seq approach that we describe here, confirms that the distal polyA isoform is indeed the precursor to the proximal polyA isoform. Therefore, unlike alternative splicing, APA sites are recognized independently, and in many cases, in a sequential manner. This provides a versatile strategy to regulate gene expression in mammalian cells.


Asunto(s)
Poli A/metabolismo , Poliadenilación , Regiones no Traducidas 3'/genética , Empalme Alternativo/genética , Células HeLa , Humanos , Intrones/genética , Matriz Nuclear/metabolismo , ARN/metabolismo , ARN Polimerasa II/metabolismo
17.
Front Cell Dev Biol ; 9: 621147, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34295886

RESUMEN

AIMS: Serine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects. METHODS: Serine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT in vitro and in vivo. In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC. RESULTS: Serine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT. CONCLUSION: Serine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.

18.
Oncol Lett ; 21(2): 79, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33363616

RESUMEN

Huntingtin interacting protein 1 (HIP1) is overexpressed in several human malignancies. However, the biological function of HIP1 in esophageal squamous cell carcinoma (ESCC), and its effect on the prognosis of patients remain unclear. The present study aimed to investigate HIP1 expression in ESCC via immunohistochemistry, reverse transcription-quantitative PCR and western blot analyses. The association between HIP1 expression and the clinicopathological characteristics of 173 patients with ESCC was statistically analyzed. The effect of HIP1 expression on patient prognosis was assessed via Kaplan-Meier and Cox regression analyses. Lentivirus-delivered RNA interfering technique was used to overexpress and downregulate HIP1 expression in ESCC cell lines. The results demonstrated that HIP1 expression was significantly higher in ESCC tissues compared with adjacent normal tissues, and HIP1 expression was associated with histological differentiation, tumor-node-metastasis stage and lymph node metastasis. Furthermore, the overall survival time of patients with high HIP1 expression was significantly shorter than those with low HIP1 expression. Cellular mobility demonstrated that overexpressing HIP1 increased ESCC proliferation, migration and invasion, whereas silencing HIP1 decreased ESCC proliferation, migration and invasion. Furthermore, overexpressing HIP1 induced ESCC cells to enter the S and G2 phases from the G1 phase, whereas HIP1 knockdown arrested the cell cycle in the G1 phase. Taken together, the results of the present study suggest that HIP1 is associated with proliferation and metastatic behaviors in ESCC, and thus may be used as a potential prognostic indicator for patients with ESCC.

19.
Front Med (Lausanne) ; 8: 573726, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34095156

RESUMEN

Background: Overseas imported cases of COVID-19 continue to increase in China, so we conducted this study to review the epidemiological characteristics of these patients. Methods: From February 26 to April 4, 2020, the imported cases from abroad were enrolled in this study. The effect of prevention countermeasures in curbing the spread of COVID-19 was assessed in this study. Moreover, we defined incubation period and confirmed time as from the date of leaving the epicenter to date of symptom onset and date of final diagnosed, respectively, and the interval of symptom onset to final diagnosed time was defined as diagnostic time. Categorical variables were summarized as numbers and percentages, and the difference among the variables were analyzed. Results: For 670 cases imported from abroad, 555 were Chinese and 115 were foreigners. Apparently, confirmed cases had significantly decreased after China was compelled to temporarily suspend the entry of foreign passport holders with valid visas or residence permits; 6 days after implement of controlled measures, the daily new confirmed cases were reduced to 13 cases. Moreover, about 84.3% of patients (166/197) presented symptoms 1 week after leaving the epicenter, and notably seven patients (3.6%) had symptoms 2 weeks after leaving the epicenter. The median incubation period was 3.0 days (inter quartile range, 1.0 to 6.0), the 95th percentile was 11.6 days. Additionally, most of cases (92.9%) were detected positively of nucleic acid after symptom onset with 4 days, the median diagnostic time was 2.0 days (interquartile range, 1.0 to 3.0), and the 95th percentile of the distribution was 5.0 days. Finally, about 5.8% of patients were healthy carriers, and the median confirmed time of asymptomatic patients was 4.0 days (interquartile range, 2.0 to 9.0). The following variables might be associated with confirmed time: symptom type (P = 0.005), exported regions (P < 0.001), and symptom onset time (P < 0.001). Conclusions: The prevention countermeasures for imported cases implemented by the Chinese government played an indispensable role in curbing the spread of COVID-19; the time of departure from epicenter could provide an estimate of the incubation period; and a confirmed time, 2-week quarantine period might need to be prolonged, while asymptomatic patients should be closely monitored.

20.
Zhong Yao Cai ; 33(11): 1689-94, 2010 Nov.
Artículo en Zh | MEDLINE | ID: mdl-21434427

RESUMEN

OBJECTIVE: To build up primary core germplasm of Scutellaria baicalensis. METHODS: The genetic diversity of 40 germplasm resources of Scutellaria baicalensis in different province were analyzed by ISSR, and the primary core germplasm were constructed with progressive sampling method of smallest genetic distance. RESULTS: 15 primers, which showed good repetitive, special bands and distinct polymorphism, were selected from 51 random ISSR primers. Then the total 248 loci were amplified by these selected 15 primers, with a 97.17% polymorphic loci. The average of Shannon information index (I), Nei's genetic diversity (H), number of alleles and effective number of alleles (NE) by POPGENE 32 analysis were 0.4353, 0.2819, 1.9640 and 1.4617, respectively. It showed there was highly genetic diversity in the 40 germplasm resources. The result of analysis by NTSYS-PC software shows the genetic similarity (Gs) were among 0.64 and 0.80, and there was upper coherence between the clustering result and source core germplasm collection except individual germplasms. The result showed the percentage of polymorphic loci was obviously reduced and the Shannon's information index and Nei's genetic diversity were increased a little, but the index change of germplasm genetic diversity was less than that before sampling. The core germplasms from No. 3 sampling were most representative, whose sampling number was about 30% of the initial sampling, and the percentage of polymorphic loci was that of before sampling 96.8%. CONCLUSIONS: It was practicable that the methods would be used to construct core germplasm collection of Scutellaria baicalensis by ISSR marker.


Asunto(s)
ADN de Plantas/genética , Variación Genética , Plantas Medicinales/genética , Secuencias Repetitivas de Ácidos Nucleicos , Scutellaria baicalensis/genética , Alelos , Análisis por Conglomerados , Conservación de los Recursos Naturales , Cartilla de ADN , Marcadores Genéticos/genética , Filogenia , Plantas Medicinales/crecimiento & desarrollo , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Scutellaria baicalensis/crecimiento & desarrollo , Especificidad de la Especie
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