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1.
J Genet Genomics ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885836

RESUMO

Phospholipase D (PLD) lipid-signaling enzyme superfamily has been widely implicated in various human malignancies, but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma (NPC). Here, we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis. Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines, correlating with worse disease-free and overall survival in NPC patients. Functional assays further elucidate PLD1's oncogenic role, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation and migration in vitro, as well as tumor growth in vivo. Notably, our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression. Specifically, PLD1 enhances NF-κB activity by facilitating the phosphorylation and nuclear translocation of RELA (p65), which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression significantly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, significantly inhibits NPC tumorigenesis in a patient-derived xenograft model. Together, our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

2.
J Med Virol ; 96(4): e29577, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572977

RESUMO

Uncovering the immune response to an inactivated SARS-CoV-2 vaccine (In-Vac) and natural infection is crucial for comprehending COVID-19 immunology. Here we conducted an integrated analysis of single-cell RNA sequencing (scRNA-seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In-Vac compared with those from COVID-19 patients. Our study reveals that In-Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In-Vac modestly upregulates IFN-α but downregulates NF-κB pathways, while natural infection triggers hyperactive IFN-α and NF-κB pathways. Both In-Vac and natural infection alter T/B cell receptor repertoires, but COVID-19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL-15RA/IL-15 receptor pathway after In-Vac boost, suggesting its potential role in enhancing In-Vac-induced immunity. Collectively, our study illuminates multifaceted immune responses to In-Vac and natural infection, providing insights for optimizing SARS-CoV-2 vaccine efficacy.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Leucócitos Mononucleares , NF-kappa B , SARS-CoV-2 , Vacinas de Produtos Inativados , Imunidade , Análise de Sequência de RNA , Anticorpos Antivirais
3.
J Clin Transl Hepatol ; 11(5): 1170-1183, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37577231

RESUMO

Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

4.
J Vis Exp ; (192)2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36847402

RESUMO

The demand for aromatic fluorides is steadily increasing in the pharmaceutical and fine chemical industries. The Balz-Schiemann reaction is a straightforward strategy for preparing aryl fluorides from aryl amines, via the preparation and conversion of diazonium tetrafluoroborate intermediates. However, significant safety risks exist in handling the aryl diazonium salts when scaling up. In order to minimize the hazard, we present a continuous flow protocol that has been successfully performed at a kilogram scale that eliminates the isolation of aryl diazonium salts while facilitating efficient fluorination. The diazotization process was performed at 10 °C with a residence time of 10 min, followed by a fluorination process at 60 °C with a residence time of 5.4 s with about 70% yield. The reaction time has been dramatically reduced by introducing this multi-step continuous flow system.


Assuntos
Fluoretos , Sais , Aminas , Halogenação
5.
Front Cell Dev Biol ; 10: 1003656, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467413

RESUMO

Background: Anti-programmed cell death 1/programmed cell death ligand 1 (PD1/PDL1) therapy is an important part of comprehensive cancer therapy. However, many patients suffer from non-response to therapy. Tumor neoantigen burden (TNB) and cancer stemness play essential roles in the responsiveness to therapy. Therefore, the identification of drug candidates for anti-PD1/PDL1 therapy remains an unmet need. Methods: Three anti-PD1/PDL1 therapy cohorts were obtained from GEO database and published literatures. Cancer immune characteristics were analyzed using CIBERSORTX, GSVA, and ESTIMATE. WGCNA was employed to identify the gene modules correlated with cancer TNB and stemness. A machine-learning method was used to construct the immunotherapy resistance score (TSIRS). Pharmacogenomic analysis was conducted to explore the potential alternative drugs for anti-PD1/PDL1 therapy resistant patients. CCK-8 assay, EdU assay and wound healing assay were used to validate the effect of the predicted drug on cancer cells. Results: The therapy response and non-response cancer groups have different microenvironment features. TSIRS was developed based on tumor neoantigen and stemness. TSIRS can effectively predict the outcomes of patients with anti-PD1/PDL1 therapy in training, validation and meta cohorts. Meanwhile, TSIRS can reflect the characteristics of tumor microenvironment during anti-PD1/PDL1 therapy. PF-4708671 is identified as a potential alternative drug for patients with resistance to anti-PD1/PDL1 therapy. It possesses significant inhibitive effect on the proliferation and migration of BGC-823 cells. Conclusion: TSIRS is an effective tool in the identification of candidate patients who will be benefit from anti-PD1/PDL1 therapy. Small molecule drug PF-4708671 has the potential to be used in anti-PD1/PDL1 therapy resistant patients.

6.
PLoS One ; 17(12): e0279621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36548308

RESUMO

BACKGROUND: Mainland China has the most smartphone users worldwide, especially among college students, while mindfulness intervention can significantly alleviate the level of problematic smartphone use. We examined the effects of a brief mindfulness intervention on problematic smartphone use and investigated if this effect is mediated by self-control. METHODS: Participants were recruited randomly from a university in Beijing of China. Forty-four college students were assigned to a mindfulness group or a control group. The mindfulness group took part in a brief (30 min) single-session mindfulness intervention. The control group was instructed to listen to a neutral news audio recording for the same duration (30 min). The Freiburg Mindfulness Inventory, Mobile Phone Addiction Tendency Scale, and Self-control Scale were used to measure state mindfulness, problematic smartphone use, and self-control of college students at pre-intervention and post-intervention, respectively. RESULTS: Two-way repeated-measures ANOVA revealed that the mindfulness group had significant improvements in state mindfulness (p = .049) and self-control (p = .012), and had significant alleviation in problematic smartphone use (p < .001) at post-intervention. In the regression model, self-control had a mediating effect between mindfulness intervention and problematic smartphone use (95% CI [0.490, 7.216]). CONCLUSIONS: A brief single-session mindfulness intervention can alleviate the level of problematic smartphone use and increase the level of state mindfulness and self-control compared to the control group. Self-control can completely mediate the efficacy of the mindfulness intervention in reducing problematic smartphone use.


Assuntos
Atenção Plena , Autocontrole , Humanos , Grupos Controle , Smartphone , Estudantes
7.
Front Microbiol ; 13: 969593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160192

RESUMO

Ex situ conservation is an important technique for protecting rare and endangered wildlife, and maintaining stable individual health is crucial to its success. Gut microbiota composition is a critical indicator of animal health and should therefore be closely monitored during ex situ conservation to track impacts on animal health. Forest musk deer (Moschus berezovskii) were historically distributed in Hebei Province, China, however, they are now extinct in the region. Thus, ex situ conservation efforts were conducted in 2016 whereby approximately 50 individuals were artificially migrated from Weinan, Shaanxi to Huailai, Hebei. To monitor gut health of these migrated individuals, we used 16S rRNA high-throughput sequencing technology to examine the microbiota differences between Huailai juvenile and Weinan juvenile groups, and between Huailai adult and Weinan adult groups. Alpha diversity analysis indicated that the richness of microbiota significantly decreased after migration to the Huailai area, and the beta diversity results also showed significant dissimilarity in gut microbial communities, demonstrating the distinct microbial structure differences in the forest musk deer population from the two areas, for both juvenile and adult groups, respectively. In addition, PICRUSt functional profile prediction indicated that the functions of gut digestion and absorption, and degradation of toxic substances were significantly weakened after ex situ conservation. Differences in diet composition between the individuals of the two sites were also observed and the impact of food on gut microbiota compositions within forest musk deer during ex situ conservation was investigated. This study provides a theoretical basis for developing ex situ conservation measures, especially for the protection of forest musk deer.

8.
J Oncol ; 2022: 4637570, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36164349

RESUMO

Colorectal cancer is the most common type of gastrointestinal malignant tumors worldwide. Standardization of the strategy for the precise treatment of this cancer has been a major challenge. Enrichment analysis of six gene groups (colon cancer-specific genes (upregulated and downregulated); rectal cancer-specific genes (upregulated and downregulated); and common genes (upregulated and downregulated)) revealed the common and specific features of colon and rectal cancer, particularly a hyperactive immune response in rectal cancer. Key common genes exhibited a similar expression pattern, but were associated with distinct patient prognosis in colon and rectal cancer. FUT4 was a core regulatory gene in rectal cancer; it can decrease the level of infiltration by M2 macrophages in the tumor immune microenvironment and participate in the positive regulation of the immune system and glycoprotein biosynthetic process, thereby affecting the outcome of patients with rectal cancer. FUT4 co-expression genes can influence patient's survival time by regulating the cell cycle. Among the regulators of FUT4 co-expression genes, checkpoint kinase 2 (CHEK2) was linked to patient outcome.

9.
BMC Genomics ; 23(1): 668, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36138352

RESUMO

BACKGROUND: Many endangered species exist in small, genetically depauperate, or inbred populations, hence promoting genetic differentiation and reducing long-term population viability. Forest Musk Deer (Moschus berezovskii) has been subject to illegal hunting for hundreds of years due to the medical and commercial values of musk, resulting in a significant decline in population size. However, it is still unclear to what extent the genetic exchange and inbreeding levels are between geographically isolated populations. By using whole-genome data, we reconstructed the demographic history, evaluated genetic diversity, and characterized the population genetic structure of Forest Musk Deer from one wild population in Sichuan Province and two captive populations from two ex-situ centers in Shaanxi Province. RESULTS: SNP calling by GATK resulted in a total of 44,008,662 SNPs. Principal component analysis (PCA), phylogenetic tree (NJ tree), ancestral component analysis (ADMIXTURE) and the ABBA-BABA test separated Sichuan and Shaanxi Forest Musk Deer as two genetic clusters, but no obvious genetic differentiation was observed between the two captive populations. The average pairwise FST value between the populations in Sichuan and Shaanxi ranged from 0.05-0.07, suggesting a low to moderate genetic differentiation. The mean heterozygous SNPs rate was 0.14% (0.11%-0.15%) for Forest Musk Deer at the genomic scale, and varied significantly among three populations (Chi-square = 1.22, p < 0.05, Kruskal-Wallis Test), with the Sichuan population having the lowest (0.11%). The nucleotide diversity of three populations varied significantly (p < 0.05, Kruskal-Wallis Test), with the Sichuan population having the lowest genetic θπ (1.69 × 10-3). CONCLUSIONS: Genetic diversity of Forest Musk Deer was moderate at the genomic scale compared with other endangered species. Genetic differentiation between populations in Sichuan and Shaanxi may not only result from historical biogeographical factors but also be associated with contemporary human disturbances. Our findings provide scientific aid for the conservation and management of Forest Musk Deer. They can extend the proposed measures at the genomic level to apply to other musk deer species worldwide.


Assuntos
Cervos , Espécies em Perigo de Extinção , Genética Populacional , Animais , China , Cervos/genética , Florestas , Metagenômica , Nucleotídeos , Filogenia
10.
Front Oncol ; 12: 953668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912218

RESUMO

Glucose, the central macronutrient, releases energy as ATP through carbon bond oxidation and supports various physiological functions of living organisms. Hepatocarcinogenesis relies on the bioenergetic advantage conferred by glucometabolic reprogramming. The exploitation of reformed metabolism induces a uniquely inert environment conducive to survival and renders the hepatocellular carcinoma (HCC) cells the extraordinary ability to thrive even in the nutrient-poor tumor microenvironment. The rewired metabolism also confers a defensive barrier which protects the HCC cells from environmental stress and immune surveillance. Additionally, targeted interventions against key players of HCC metabolic and signaling pathways provide promising prospects for tumor therapy. The active search for novel drugs based on innovative mutation targets is warranted in the future for effectively treating advanced HCC and the preoperative downstage. This article aims to review the regulatory mechanisms and therapeutic value of glucometabolic reprogramming on the disease progression of HCC, to gain insights into basic and clinical research.

11.
Genes (Basel) ; 13(5)2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35627313

RESUMO

Major histocompatibility complex (MHC) genes are the most polymorphic in vertebrates and the high variability in many MHC genes is thought to play a crucial role in pathogen recognition. The MHC class II locus DQA polymorphism was analyzed in the endangered Przewalski's horse, Equus przewalskii, a species that has been extinct in the wild and all the current living individuals descend from 12 founders. We used the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) to detect the polymorphism within the MHC DQA in 31 Przewalski's horses from two reintroduced populations. Consequently, only seven alleles were identified, with only four presenting in each population. In comparison with other mammals, the Przewalski's horse demonstrated less MHC variation. The nucleotide genetic distance of the seven ELA-DQA alleles was between 0.012 and 0.161. The Poisson corrected amino acid genetic distance of the founded alleles was 0.01-0.334. The allele and genotype frequencies of both reintroduced populations of Przewalski's horse deviated from the Hardy-Weinberg equilibrium. Specific MHC DQA alleles may have been lost during the extreme bottleneck event that this species underwent throughout history. We suggest the necessity to detect the genetic background of individuals prior to performing the reintroduction project.


Assuntos
Antígenos de Histocompatibilidade Classe II , Complexo Principal de Histocompatibilidade , Alelos , Animais , Antígenos de Histocompatibilidade Classe II/genética , Cavalos/genética , Complexo Principal de Histocompatibilidade/genética , Mamíferos/genética , Polimorfismo Conformacional de Fita Simples
12.
Cancer Immunol Immunother ; 71(3): 689-703, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34365516

RESUMO

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov ; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn ). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients' CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. Précis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts < 5% can benefit from consolidative allo-HSCT post-CAR-T therapy.


Assuntos
Antígenos CD19 , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores de Antígenos Quiméricos , Adolescente , Adulto , Antígenos CD19/imunologia , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Síndrome da Liberação de Citocina/etiologia , Gerenciamento Clínico , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Doenças do Sistema Nervoso/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Prognóstico , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos/imunologia , Adulto Jovem
13.
J Steroid Biochem Mol Biol ; 217: 106026, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34808361

RESUMO

The scent (musk) gland is an organ unique to muskrats and other scent-secreting animals, and the pheromones (musk) synthesized and secreted by the scent gland play a role in chemical communication among scent-secreting animals. The musk gland is synchronized with testicular developmental changes; however, little is known regarding androgen secretion from the testis and how this regulates pheromone synthesis and the secretion of scent. To investigate the effect of androgens on the synthesis of pheromones in the musk gland, we established a muskrat castration model by surgical removal of the testis, and analyzed the histomorphology, hormone concentration, gene expression, and changes in the chemical composition of the musk gland in castration and control groups by histomorphological analysis, Enzyme-Linked ImmunoSorbent Assay (ELISA), RNA sequencing (RNA-seq), and gas chromatography-mass spectrometry (GCMS). Histomorphological analysis results showed that after castration, muskrat gland cells underwent significant atrophy (P < 0.05). Hormone measurement results showed that there was a significant decrease in serum testosterone and muskrat musk testosterone (P < 0.05) after muskrat castration. Transcriptome sequencing results showed that 510 differentially expressed transcripts (DETs) were mainly enriched in fatty acid metabolism, terpenoid backbone biosynthesis, fatty acid degradation, PPAR signaling pathway, and fatty acid biosynthesis. GCMS results showed that macrocyclic ketones, steroids, fatty acids, alcohols, and esters in musk were significantly changed (P < 0.05). In conclusion, androgens were found to play an important function in the chemical communication exchange between muskrats through regulating pheromone synthesis in musk cells. This study provides a basis for understanding the mechanism of animal communication influenced by androgens.


Assuntos
Androgênios , Glândulas Odoríferas , Androgênios/metabolismo , Animais , Arvicolinae/genética , Masculino , Feromônios/metabolismo , Glândulas Odoríferas/metabolismo , Estações do Ano , Testosterona/metabolismo
15.
Front Oncol ; 11: 714665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540684

RESUMO

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. In view of the lack of early obvious clinical symptoms and related early diagnostic biomarkers with high specificity and sensitivity, most HCC patients are already at the advanced stages at the time of diagnosis, and most of them are accompanied by distant metastasis. Furthermore, the unsatisfactory effect of the follow-up palliative care contributes to the poor overall survival of HCC patients. Therefore, it is urgent to identify effective early diagnosis and prognostic biomarkers and to explore novel therapeutic approaches to improve the prognosis of HCC patients. Circular RNA (CircRNA), a class of plentiful, stable, and highly conserved ncRNA subgroup with the covalent closed loop, is dysregulated in HCC. Increasingly, emerging evidence have confirmed that dysregulated circRNAs can regulate gene expression at the transcriptional or post-transcriptional level, mediating various malignant biological behaviors of HCC cells, including proliferation, invasion, metastasis, immune escape, stemness, and drug resistance, etc.; meanwhile, they are regarded as potential biomarkers for early diagnosis and prognostic evaluation of HCC. This article reviews the research progress of circRNAs in HCC, expounding the potential molecular mechanisms of dysregulated circRNAs in the carcinogenesis and development of HCC, and discusses those application prospects in the diagnosis and prognosis of HCC.

16.
Biomed Pharmacother ; 138: 111529, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311529

RESUMO

Hepatocellular carcinoma (HCC) has become a challenging disease in the world today. Due to the limitations on the current diagnosis and treatment as well as its high metastatic ability and high recurrence rate, HCC gradually becomes the second deadliest tumor. Exosomes are one of the types of cell-derived vesicles and can carry intracellular materials such as genetic materials, lipids, and proteins. In recent years, it has been verified that exosomes are linked to numerous physiological and pathological processes, including HCC. However, how exosomes affect HCC progression remains largely unknown. In this review, the exosome-mediated cellular material transfer between cells of different types in the HCC microenvironment and their effects on the behaviors and functions of recipient cells are studied. Furthermore, we also addressed the underlying molecular mechanisms. We believe that new light on the diagnosis of this cancer as well as its treatment strategies will be shed after a collation of literature in this area.


Assuntos
Carcinoma Hepatocelular/metabolismo , Comunicação Celular , Exossomos/metabolismo , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Portadores de Fármacos , Exossomos/genética , Exossomos/patologia , Exossomos/transplante , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Valor Preditivo dos Testes , Transdução de Sinais
17.
J Genet Genomics ; 48(7): 595-605, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34274258

RESUMO

RNA binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers but scarcely studied in nasopharyngeal carcinoma (NPC). Here, we compare the mRNA levels of 29 RBMs between 87 NPC and 10 control samples. We find that RBM47 is frequently upregulated in NPC specimens, and its high expression is associated with the poor prognosis of patients with NPC. Biological experiments show that RBM47 plays an oncogenic role in NPC cells. Mechanically, RBM47 binds to the promoter and regulates the transcription of BCAT1, and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells. Moreover, transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-mRNA, including those cancer-related, to a large extent in NPC cells. Furthermore, RBM47 binds to hnRNPM and cooperatively regulates multiple splicing events in NPC cells. In addition, we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells. Our study, taken together, shows that RBM47 promotes the progression of NPC through multiple pathways, acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM. Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC.


Assuntos
Carcinoma Nasofaríngeo
18.
Biomed Pharmacother ; 141: 111889, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34323697

RESUMO

Long non-coding RNA (lncRNA), a subgroup of ncRNA with a length of more than 200 nt without protein coding function, has been recognized by the academia for its mediating effects of dysregulated expression on the tumorigenesis and development of a variety of tumors. LncRNA DiGeorge syndrome critical region gene 5 (DGCR5), originally found to induce DiGeorge syndrome, has been confirmed to be extremely dysregulated in multiple tumors, which mediates the malignant phenotypes of hepatocellular carcinoma, pancreatic cancer, lung cancer, etc. through the regulation of Wnt/ß-catenin, MEK/ERK1/2 and other cancerous signaling pathways as a molecular sponge. Researches on the cancerous derivation-related pathways involved in DGCR5 can provide potential molecular intervention targets for tumor precision treatment. Moreover, liquid biopsy based on the detection of DGCR5 in body fluids is also expected to provide a non-invasive evaluation method for the early diagnosis and prognostic evaluation of malignant tumors.


Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Síndrome de DiGeorge/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Animais , Apoptose/fisiologia , Biomarcadores Tumorais/biossíntese , Carcinogênese/metabolismo , Proliferação de Células/fisiologia , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/metabolismo , RNA Longo não Codificante/biossíntese
19.
Adv Sci (Weinh) ; 8(16): e2004852, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34180133

RESUMO

20-30% of patients with nasopharyngeal carcinoma (NPC) develop distant metastasis or recurrence leading to poor survival, of which the underlying key molecular events have yet to be addressed. Here alternative splicing events in 85 NPC samples are profiled using transcriptome analysis and it is revealed that the long isoform of GOLIM4 (-L) with exon-7 is highly expressed in NPC and associated with poor prognosis. Lines of evidence demonstrate the pro-tumorigenic function of GOLIM4-L in NPC cells. It is further revealed that RBFOX2 binds to a GGAA motif in exon-7 and promotes its inclusion forming GOLIM4-L. RBFOX2 knockdown suppresses the tumorigenesis of NPC cells, phenocopying GOLIM4-L knockdown, which is significantly rescued by GOLIM4-L overexpression. High expression of RBFOX2 is correlated with the exon-7 inclusion of GOLIM4 in NPC biopsies and associated with worse prognosis. It is observed that RBFOX2 and GOLIM4 can influence vesicle-mediated transport through maintaining the organization of Golgi apparatus. Finally, it is revealed that RAB26 interacts with GOLIM4 and mediates its tumorigenic potentials in NPC cells. Taken together, the findings provide insights into how alternative splicing contributes to NPC development, by highlighting a functional link between GOLIM4-L and its splicing regulator RBFOX2 activating vesicle-mediated transport involving RAB26.


Assuntos
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Fatores de Processamento de RNA/genética , Splicing de RNA/genética , Proteínas Repressoras/genética , Proteínas de Transporte Vesicular/genética , Humanos
20.
Artigo em Inglês | MEDLINE | ID: mdl-34122602

RESUMO

BACKGROUND: Flow is characterized by the strong concentration in competitions, eliminating irrelevant thoughts and emotions, integrating all tasks, and continuing the competition smoothly even in challenging situations. The present study was into whether or not brief mindfulness training can improve athletes' flow and further explore the mediating effect of resilience in the intervention. METHODS: The 2 (experimental conditions) × 2 (time) mixed design was used in this study. Fifty-seven student-athletes were recruited and randomly assigned into either a brief mindfulness group (n = 29) or a control group (n = 28). Before and after the intervention, every participant completed a self-report measure including mindfulness, flow, and resilience. RESULTS: Participants in the brief mindfulness group showed increased mindfulness, flow, and resilience (p < 0.001) after brief mindfulness training; when putting resilience change (B = 0.30, 95% CI [0.031, 0.564]) into the equation, the direct (95% CI [3.156, 13.583]) and indirect (95% CI [0.470, 5.048]) effects of mindfulness training were both significant. CONCLUSION: It was concluded that brief mindfulness training could significantly improve athletes' flow and resilience, and resilience partly mediated the effects of brief mindfulness training on flow.

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