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1.
Anal Chim Acta ; 1189: 339210, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815051

RESUMO

Circular Ribonucleic Acid (CircRNA) plays regulatory roles in many biological processes, such as tumors and metabolic diseases. Due to the fact that circRNA is more stable and conservative than linear RNA, circRNA has become a potential biomarker in early clinical diagnosis and biomedical research. Therefore, the quantification of circRNA expression level is of importance for understanding their functions and their applications for disease diagnosis and treatment. Nevertheless, due to the low abundance of circRNA, it is still a challenge for the analysis of circRNA in cells. Herein, we proposed a sensitive detection method for circRNA based on the T7 exonuclease-assisted cycling enzymatic amplification. The fluorescent sensor was constructed by a hairpin molecular beacon and T7 exonuclease. With the cycling enzymatic amplification process, this sensor achieved the limit of detection of 1 pM with a good linear correlation in the range of 0-100 pM (R2 = 0.9891) using circBART2.2 as a model. Furthermore, we applied the proposed method in the determination of circBART2.2 in cell lysates. The results demonstrated that this method has promising applications in early diagnosis of Epstein-Barr virus (EBV) infection-related diseases using circRNA as the biomarker.


Assuntos
Infecções por Vírus Epstein-Barr , RNA Circular , Contagem de Células , Herpesvirus Humano 4 , Humanos , Limite de Detecção , Espectrometria de Fluorescência
2.
Am J Cancer Res ; 11(10): 4642-4667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765285

RESUMO

In eukaryotes, alternative splicing refers to a process via which a single precursor RNA (pre-RNA) is transcribed into different mature RNAs. Thus, alternative splicing enables the translation of a limited number of coding genes into a large number of proteins with different functions. Although, alternative splicing is common in normal cells, it also plays an important role in cancer development. Alteration in splicing mechanisms and even the participation of non-coding RNAs may cause changes in the splicing patterns of cancer-related genes. This article reviews the latest research on alternative splicing in cancer, with a view to presenting new strategies and guiding future studies related to pathological mechanisms associated with cancer.

3.
Front Cell Dev Biol ; 9: 762796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805170

RESUMO

Immunotherapy, including immune checkpoint blockade and chimeric antigen receptor T cells, is one of the most promising approaches to treat cancer. Vaccines have been effective in preventing cancers like liver cancer and cervical cancer with a viral etiology. Instead of preventing disease, therapeutic cancer vaccines mobilize the immune system to attack existing cancer. p53 is dysregulated in the majority of human cancers and is a highly promising target for cancer vaccines. Over twenty clinical trials have targeted p53 in malignant diseases using vaccines. In this work, we review the progress of vaccinations with p53 or its peptides as the antigens and summarize the clinical and immunological effects of p53-targeting vaccines from clinical trials. The delivery platforms include p53 peptides, viral vectors, and dendritic cells pulsed with short peptides or transduced by p53-encoding viruses. These studies shed light on the feasibility, safety, and clinical benefit of p53 vaccination in select groups of patients, implicating that p53-targeting vaccines warrant further investigations in experimental animals and human studies.

4.
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.

5.
Oncogene ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725462

RESUMO

Nasopharyngeal carcinoma (NPC) demonstrates significant regional differences and a high incidence in Southeast Asia and Southern China. Bactericidal/permeability-increasing-fold- containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. BPIFB1 expression is substantially downregulated in NPC and is significantly associated with poor prognosis in patients with NPC. However, the specific molecular mechanism by which BPIFB1 regulates NPC is not well understood. In this study, we found that BPIFB1 inhibits vasculogenic mimicry by regulating the metabolic reprogramming of NPC. BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 signaling pathway. Altered glycolysis reduces the acetylation level of histone and decreases the expression of vasculogenic mimicry-related genes, VEGFA, VE-cadherin, and MMP2, ultimately leading to the inhibition of vasculogenic mimicry. To our knowledge, this is the first report on the role and specific mechanism of BPIFB1 as a tumor suppressor gene involved in regulating glycolysis and vasculogenic mimicry in NPC. Overall, these results provide a new therapeutic target for NPC diagnosis and treatment.

7.
BMC Microbiol ; 21(1): 265, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607559

RESUMO

BACKGROUND: Preeclampsia (PE) is a condition of high blood pressure that is usually concurrent with proteinuria in pregnancy. PE complicates the management of both maternal and fetal health and contributes to most adverse pregnancy outcomes, but the mechanism underlying the development of PE remains unclear. In this study, we performed a case-control study to compare the gut microbiota of PE (n = 26), abnormal placental growth (APG, n = 25) and healthy pregnant women (n = 28) and analyzed the potential pathogenic role of gut microbiota in PE progression. RESULTS: The clinical pathophysiological state did not affect the bacterial diversity, while the compositions of the gut microbiota were significantly altered in both the PE and APG groups compared with healthy pregnant women. At the phylum level, TM7 was significantly increased in women with APG. Heterogeneity was observed at the genus level, especially in genera with positive LDA scores, suggesting the stage-dependent effect of gut microbiota on the development of PE. The beneficial bacterium Lactobacillus was markedly depleted in the PE and APG groups but was only correlated with blood pressure (BP) and proteinuria levels in the PE group. Two different bacterial taxa belonged to Lactobacillus showed different correlations (OTU255 and OTU784 were significantly related to PE and APG, respectively). CONCLUSIONS: Our results indicated that shifts in the gut microbiota might occur from the early stages of the development of PE, which is of possible etiological and therapeutic importance.

10.
J Cancer ; 12(20): 6216-6230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539895

RESUMO

The Hippo signaling pathway is a relatively young tumor-related signaling pathway. Although it was discovered lately, research on it developed rapidly. The Hippo signaling pathway is closely relevant to the occurrence and development of tumors and the maintenance of organ size and other biological processes. This manuscript focuses on YAP, the core molecule of the Hippo signaling pathway, and discussion the upstream and downstream regulatory networks of the Hippo signaling pathway during tumorigenesis and development. It also summarizes the relevant drugs involved in this signaling pathway, which may be helpful to the development of targeted drugs for cancer therapy.

11.
Mol Cancer ; 20(1): 112, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465340

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are widely expressed in human cells and are closely associated with cancer development. However, they have rarely been investigated in the context of nasopharyngeal carcinoma (NPC). METHODS: We screened a new circRNA, circRNF13, in NPC cells using next-generation sequencing of mRNA. Reverse transcription polymerase chain reaction and RNA fluorescence in situ hybridization were used to detect circRNF13 expression in 12 non-tumor nasopharyngeal epithelial (NPE) tissues and 36 NPC samples. Cell proliferation was detected using MTT and flow cytometry assays, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. Cell glycolysis was analyzed using the Seahorse glycolytic stress test. Glucose transporter type 1 (GLUT1) ubiquitination and SUMOylation modifications were analyzed using co-immunoprecipitation and western blotting. CircRNF13 and Small Ubiquitin-like Modifier 2 (SUMO2) interactions were analyzed using RNA pull-down and luciferase reporter assays. Finally, to test whether circRNF13 inhibited NPC proliferation and metastasis in vivo, we used a xenograft nude mouse model generated by means of subcutaneous or tail vein injection. RESULTS: We found that circRNF13 was stably expressed at low levels in NPC clinical tissues and NPC cells. In vitro and in vivo experiments showed that circRNF13 inhibited NPC proliferation and metastasis. Moreover, circRNF13 activated the SUMO2 protein by binding to the 3'- Untranslated Region (3'-UTR) of the SUMO2 gene and prolonging the half-life of SUMO2 mRNA. Upregulation of SUMO2 promotes GLUT1 degradation through SUMOylation and ubiquitination of GLUT1, which regulates the AMPK-mTOR pathway by inhibiting glycolysis, ultimately resulting in the proliferation and metastasis of NPC. CONCLUSIONS: Our results revealed that a novel circRNF13 plays an important role in the development of NPC through the circRNF13-SUMO2-GLUT1 axis. This study implies that circRNF13 mediates glycolysis in NPC by binding to SUMO2 and provides an important theoretical basis for further elucidating the pathogenesis of NPC and targeted therapy.

12.
Environ Toxicol ; 36(12): 2448-2453, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34459104

RESUMO

Rheumatoid arthritis (RA) is one of the inflammatory diseases detected in more than 1% of the world population. In the present study, oxymatrine hydrazone (OMTH) was synthesized and investigated for treatment of RA in vitro in TNF-α induced fibroblast-like synoviocyte cell model. Cell viability and apoptosis were detected using MTT and flow cytometry assays, respectively. ELISA was used for determination of inflammatory cytokines and western blotting for evaluation of protein expression. Pretreatment of HFLS-RA cells with 0.5, 1.0, 1.5, 2.0, and 2.5 µM doses of OMTH suppressed TNF-α induced promotion of proliferative potential in dose-based manner. The OMTH pretreatment of TNF-α exposed HFLS-RA cells significantly increased apoptotic cell proportion. In TNF-α exposed HFLS-RA cells OMTH pretreatment elevated Bax and suppressed Bcl-2 expression. Treatment of HFLS-RA cells with OMTH prevented TNF-α mediated elevation of IL-1ß, IL-6 and IL-8. Moreover, OMTH treatment of HFLS-RA cells effectively suppressed TNF-α mediated elevated levels of MMP-1 and MMP-13. Pretreatment of HFLS-RA cells with OMTH reversed TNF-α mediated promotion of iNOS and COX-2 levels. The MEK/1/2 and p65 phosphorylation in TNF-α exposed HFLS-RA cells was reduced by OMTH pre-treatment in dose-based manner. Thus, OMTH successfully inhibited TNF-α-mediated increased viability of RA synovial cells and activated apoptosis. Pretreatment of TNF-α exposed synovial cells with OMTH targeted phosphorylation of MEK/NF-κB. Therefore, OMTH may act as potential therapeutic agent for RA treatment.


Assuntos
Artrite Reumatoide , NF-kappa B , Alcaloides , Artrite Reumatoide/tratamento farmacológico , Células Cultivadas , Regulação para Baixo , Fibroblastos/metabolismo , Humanos , Hidrazonas/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno , NF-kappa B/metabolismo , Quinolizinas , Fator de Necrose Tumoral alfa
13.
IEEE Trans Image Process ; 30: 6637-6647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280100

RESUMO

The defect detection task can be regarded as a realistic scenario of object detection in the computer vision field and it is widely used in the industrial field. Directly applying vanilla object detector to defect detection task can achieve promising results, while there still exists challenging issues that have not been solved. The first issue is the texture shift which means a trained defect detector model will be easily affected by unseen texture, and the second issue is partial visual confusion which indicates that a partial defect box is visually similar with a complete box. To tackle these two problems, we propose a Reference-based Defect Detection Network (RDDN). Specifically, we introduce template reference and context reference to against those two problems, respectively. Template reference can reduce the texture shift from image, feature or region levels, and encourage the detectors to focus more on the defective area as a result. We can use either well-aligned template images or the outputs of a pseudo template generator as template references in this work, and they are jointly trained with detectors by the supervision of normal samples. To solve the partial visual confusion issue, we propose to leverage the carried context information of context reference, which is the concentric bigger box of each region proposal, to perform more accurate region classification and regression. Experiments on two defect detection datasets demonstrate the effectiveness of our proposed approach.

15.
Front Cell Dev Biol ; 9: 616784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195184

RESUMO

Breast cancer is the most common malignant tumor in women, and its incidence is increasing each year. To effectively treat breast cancer, it is important to identify genes involved in its occurrence and development and to exploit them as potential drug therapy targets. Here, we found that potassium channel subfamily K member 6 (KCNK6) is significantly overexpressed in breast cancer, however, its function in tumors has not been reported. We further verified that KCNK6 expression is upregulated in breast cancer biopsies. Moreover, overexpressed KCNK6 was found to enhance the proliferation, invasion, and migration ability of breast cancer cells. These effects may occur by weakening cell adhesion and reducing cell hardness, thus affecting the malignant phenotype of breast cancer cells. Our study confirmed, for the first time, that increased KCNK6 expression in breast cancer cells may promote their proliferation, invasion, and migration. Moreover, considering that ion channels serve as therapeutic targets for many small molecular drugs in clinical treatment, targeting KCNK6 may represent a novel strategy for breast cancer therapies. Hence, the results of this study provide a theoretical basis for KCNK6 to become a potential molecular target for breast cancer treatment in the future.

16.
Cancer Res ; 81(19): 5074-5088, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34321242

RESUMO

Epstein-Barr virus (EBV) infection is an established cause of nasopharyngeal carcinoma (NPC) and is involved in a variety of malignant phenotypes, including tumor immune escape. EBV can encode a variety of circular RNAs (circRNA), however, little is known regarding the biological functions of these circRNAs in NPC. In this study, EBV-encoded circBART2.2 was found to be highly expressed in NPC where it upregulated PD-L1 expression and inhibited T-cell function in vitro and in vivo. circBART2.2 promoted transcription of PD-L1 by binding the helicase domain of RIG-I and activating transcription factors IRF3 and NF-κB, resulting in tumor immune escape. These results elucidate the biological function of circBART2.2, explain a novel mechanism of immune escape caused by EBV infection, and provide a new immunotherapy target for treating NPC. SIGNIFICANCE: This work demonstrates that circBART2.2 binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma.

17.
J Mater Chem B ; 9(33): 6553-6575, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34328147

RESUMO

Carbon dots (CDs) are a new type of carbon nanomaterial that have unique physical and chemical properties, good biocompatibility, low toxicity, and easy surface functionalization, making them widely used in biological imaging, environmental monitoring, chemical analysis, targeted drug delivery, disease diagnosis, therapy, etc. In this review, our content is mainly divided into four parts. In the first part, we focused on the preparation methods of CDs, including arc discharge, laser ablation, electrochemical oxidation, chemical oxidation, combustion, hydrothermal/solvent thermal, microwave, template, method etc. Next, we summarized methods of CD modification, including heteroatom doping and surface functionalization. Then, we discussed the optical properties of CDs (ultraviolet absorption, photoluminescence, up-conversion fluorescence, etc.). Lastly, we reviewed the common applications of CDs in biomedicine from the aspects of in vivo and in vitro imaging, sensors, drug delivery, cancer theranostics, etc. Furthermore, we also discussed the existing problems and the future development direction of CDs.

18.
DNA Cell Biol ; 40(8): 1052-1063, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34191589

RESUMO

Gossypol has been reported to exhibit antitumor effects against several human cancers. However, the anticancer effects of gossypol on nasopharyngeal carcinoma (NPC) have not been investigated. Against this backdrop, the present study was designed to evaluate the anticancer effects of gossypol against NPC cells and to identify the signaling pathways involved through bioinformatic analysis. Gossypol-inhibited death of NPC cells is concentration-dependent. To explore the underlying mechanism for gossypol's antitumor effect, microarray of gossypol-treated and -untreated NPC cells was performed. A total of 836 differentially expressing genes (DEGs) were identified in gossypol-treated NPC cells, of which 461 genes were upregulated and 375 genes were downregulated. The cellular components, molecular functions, biological processes, and signal pathways, in which the DEGs were involved, were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The Gene Set Enrichment Analysis (GSEA) predicted upstream transcription factors (TF) ETS2 and E2F1 that regulate DEGs. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify a class of modules and genes related to DNA repair and cell cycle. TNFRSF10B, a receptor for death in NPC cells, was knocked down. The results suggested that the ability of NPC cells to resist gossypol killing was enhanced. In addition, to further investigate the possible molecular mechanisms, we constructed a transcriptional regulatory network of TNFRSF10B containing 109 miRNAs and 47 TFs. Taken together, our results demonstrated that gossypol triggered antitumor effects against NPC cells, indicating its applicability for the management of NPC.


Assuntos
Antineoplásicos/farmacologia , Redes Reguladoras de Genes , Gossipol/farmacologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Transcriptoma , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
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.

20.
J Exp Clin Cancer Res ; 40(1): 190, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108030

RESUMO

BACKGROUND: Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and is a potential cancer treatment strategy. Triptolide (TPL) is a natural product isolated from the traditional Chinese herb which possesses potent anti-tumor activity in human cancers. However, its role in pyroptosis remains to be elucidated. METHODS: Cell survival was measured by colony formation assay. Cell apoptosis was determined by Annexin V assay. Pyroptosis was evaluated by morphological features and release of interleukin 1ß and lactate dehydrogenase A (LDHA). Immunofluorescence staining was employed to measure subcellular localization of proteins. Tumorigenicity was assessed by a xenograft tumor model. Expression levels of mRNAs or proteins were determined by qPCR or western blot assay, respectively. RESULTS: Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates the cytotoxicity of TPL against cancer cells. TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3. Silencing HK-II sensitizes cancer cells to TPL induced pyroptosis, whereas enforced expression of HK-II prevents TPL induced pyroptosis. Mechanistically, HK-II prevents mitochondrial translocation of BAD, BAX proteins and activation of caspase 3, thus attenuating cleavage of GSDME and pyroptosis upon TPL treatment. Furthermore, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME. Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model. CONCLUSIONS: This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis.

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