RESUMO
BACKGROUND: The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N6-methyladenosine (m6A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. METHODS: The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. RESULTS: METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m6A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. CONCLUSIONS: This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment.
Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Metiltransferases , MicroRNAs , RNA Longo não Codificante , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metiltransferases/genética , Metiltransferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Colorectal cancer (CRC) is a common malignancy with significant prevalence and mortality rates. Circular RNA FOXO3 (circFOXO3; hsa_circ_0006404) has been reported to be involved in cancer regulation; however, its role in CRC is yet to be fully elucidated. Therefore, the aim of the present study was to investigate the effect of circFOXO3 on CRC progression and identify its underlying mechanism. In the present study, the expression of circFOXO3 was investigated in CRC tissues and cells via reverse transcriptionquantitative PCR. A Cell Counting Kit8 and colony formation assays were used to assess cell proliferation. The cell migratory and invasive abilities were detected using the Transwell migration and invasion assays. The luciferase assay and RNA pulldown assay were conducted to verify the relationship of circFOXO3, microRNA (miR)543 and Large tumor suppressor kinase 1 (LATS1). The results demonstrated that circFOXO3 expression was downregulated in CRC tissues and cells, and was associated with poor overall survival of patients with CRC. Moreover, circFOXO3 was associated with tumor size, distant metastasis, differentiation, lymph node metastasis and TMN stages of patients with CRC. circFOXO3 overexpression suppressed CRC cell proliferation, migration and invasion. Luciferase assay and RNA pulldown assay results indicated that circFOXO3 functioned as a sponge for miR543. In addition, circFOXO3 increased the expression of LATS1 via sponging miR543, thus inhibiting CRC cell aggressive features. Collectively, the present results suggested that circFOXO3 inhibited CRC metastasis and progression via elevated LATS1 expression by sponging miR543. Therefore, circFOXO3 may be a promising target for CRC therapy.
Assuntos
Neoplasias Colorretais/metabolismo , Proteína Forkhead Box O3/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Glioma is one of the most common malignancies of the nervous system. Long noncoding RNAs (lncRNAs) are regulators involved in the progression of tumors. The present study aimed to determine the role of lncRNA cancer susceptibility 19 (CASC19) in glioma and its underlying molecular mechanism. Reverse transcriptionquantitative PCR was performed to detect CASC19 and microRNA (miR)4543p expression in glioma and normal brain tissues. Rasrelated protein in brain 5A (RAB5A) expression in glioma cells was also analyzed via western blotting. The relationship between CASC19 expression, clinicopathological parameters and MRI characteristics in patients with glioma was analyzed. Cell Counting Kit8, BrdU, wound healing and Transwell assays were adopted to detect glioma cell proliferation, migration and invasion, respectively. The dualluciferase reporter gene and RNA immunoprecipitation experiments were conducted to verify the targeting relationship between CASC19 and miR4543p, and between miR4543p and RAB5A. The results revealed that CASC19 expression was significantly upregulated in glioma tissues and cell lines. CASC19 expression was also positively associated with tumor diameter and pathological grade. Additionally, its high expression was closely associated with tumor MRI signal heterogeneity and peritumoral edema. CASC19 upregulation promoted glioma cell proliferation and metastasis, while CASC19knockdown demonstrated the opposite effect. CASC19 sponged miR4543p, which indirectly increased RAB5A expression. The results demonstrated that the CASC19/miR4543p/RAB5A axis is involved in the promotion of glioma progression.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas rab5 de Ligação ao GTP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/diagnóstico , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Regulação para CimaRESUMO
PURPOSE: To develop and internally validate nomograms to help choose the optimal biopsy strategy among no biopsy, targeted biopsy (TB) only, or TB plus systematic biopsy (SB). PATIENTS AND METHODS: This retrospective study included a total of 385 patients who underwent magnetic resonance imaging (MRI)-guided TB and/or SB at our institute after undergoing multiparametric MRI (mpMRI) between 2015 and 2018. We developed models to predict clinically significant prostate cancer (csPCa) based on suspicious lesions from a TB result and based on the whole prostate gland from the results of TB plus SB or SB only. Nomograms were generated using logistic regression and evaluated using receiver-operating characteristic (ROC) curve analysis, calibration curves and decision analysis. The results were validated using ROC curve and calibration on 177 patients from 2018 to 2019 at the same institute. RESULTS: In the multivariate analyses, prostate-specific antigen level, prostate volume, and the Prostate Imaging Reporting and Data System score were predictors of csPCa in both nomograms. Age was also included in the model for suspicious lesions, while obesity was included in the model for the whole gland. The area under the curve (AUC) in the ROC analyses of the prediction models was 0.755 for suspicious lesions and 0.887 for the whole gland. Both models performed well in the calibration and decision analyses. In the validation cohort, the ROC curve described the AUCs of 0.723 and 0.917 for the nomogram of suspicious lesions and nomogram of the whole gland, respectively. Also, the calibration curve detected low error rates for both models. CONCLUSION: Nomograms with excellent discriminative ability were developed and validated. These nomograms can be used to select the optimal biopsy strategy for individual patients in the future.
Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Nomogramas , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Técnicas de Apoio para a Decisão , Humanos , Biópsia Guiada por Imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/análise , Curva ROC , Estudos RetrospectivosRESUMO
A cognitive magnetic resonance imaging (MRI)-targeted prostate biopsy conducted by an experienced clinician enhances the detection rate of (high-grade) prostate cancer; however, this method is less successful in the hands of inexperienced surgeons. Therefore, an alternative method of conducting a cognitive MRI-targeted biopsy that can be successfully performed by the inexperienced clinicians should be developed. Ninety-six males suspected of prostate cancer were analyzed using systematic biopsy and cognitive MRI-targeted biopsy based on our novel three-dimensional matrix positioning method. Typically, the core principle of the latter procedure was to put the MRI and ultrasound images into the same virtual coordinate system. Afterward, the targeted biopsy was transformed to target a coordinate for the suspected lesion in the MRI. Subsequently, patients were assessed for the presence/absence of prostate cancer or high-grade prostate cancer. According to our results, the overall detection rate of prostate cancer was 70.8% (68/96), and the detection rate of high-grade prostate cancer was 56.3% (54/96). Specifically, the detection rate of prostate cancer by systematic biopsy was 54.2% (52/96) and that by targeted biopsy was 59.4% (57/96; P = 0.560). Clearly, the combined application of targeted biopsy could remarkably increase the detection rates of prostate cancer (P = 0.025) and high-grade prostate cancer (P = 0.009). Taken together, the findings of this study suggest that the combination of systematic biopsy with our three-dimensional matrix positioning-driven cognitive-targeted biopsy is superior to systematic biopsy in detecting prostate cancer and high-grade prostate cancer.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Períneo , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Software , UltrassonografiaRESUMO
Two new xanthones (1-2), together with four known ones (3-6), were isolated from whole herb of Swertia elata. Their structures were elucidated by spectroscopic methods including extensive 1D- and 2D-NMR techniques. Their anti-tobacco mosaic virus (anti-TMV) activity test revealed that 1-6 showed weak anti-TMV activities with inhibition rate in the range of 15.2-28.8% at the concentration of 20 µM.
Assuntos
Swertia/química , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Xantonas/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Xantonas/química , Xantonas/farmacologiaRESUMO
INTRODUCTION: Sexual curiosity and the quest for sexual excitement are the most frequent reasons for patients to introduce foreign bodies into the urethra or the bladder. Imagination and surgical skill are essential for urologists to retrieve such vesical foreign bodies. AIM: The aim of this study was to describe a novel method for retrieving vesical magnetic beads, which were inserted for autoeroticism by a male adolescent, with a self-made "magnetic sheath." METHODS: A 21-year-old young man inserted more than one hundred small magnetic beads into his urethra for sexual excitement, which lately caused symptoms of gross hematuria, frequent urination, and acute lower abdominal pain when walking or urinating. We invented a magnetic sheath by fixing a magnetic bead on the tip of an F9.5 ureteral access sheath to remove the foreign bodies in a minimally invasive way. MAIN OUTCOME MEASURE: The feasibility of using magnetic sheath to remove vesical foreign bodies; and operation duration. RESULTS: Under direct visualization of an F8/9.8 ureteroscope, the magnetic sheath could firmly attach to the magnetic bead inside the bladder and could easily pull out 5 to 15 beads each time. It took about 5 minutes to remove all of the 125 magnetic beads by utilizing our magnetic sheath. CONCLUSIONS: The self-made magnetic sheath can make the task of removal of magnetic foreign bodies easy to urologists, requiring less time and surgical skills. The new equipment provides a new method for urologists to deal with the challenging task of removing metal vesical foreign bodies which were self-inserted for masturbation.
Assuntos
Corpos Estranhos/complicações , Corpos Estranhos/cirurgia , Migração de Corpo Estranho/complicações , Prepúcio do Pênis/lesões , Fenômenos Magnéticos , Imãs/efeitos adversos , Uretra/lesões , Doenças da Bexiga Urinária/etiologia , Adolescente , Migração de Corpo Estranho/cirurgia , Humanos , Masculino , Masturbação , Procedimentos Cirúrgicos Minimamente Invasivos , Comportamento Sexual , Resultado do Tratamento , Doenças da Bexiga Urinária/cirurgia , Adulto JovemRESUMO
OBJECTIVE: In this study, the clinical effect of the Nd: YAG laser embolysis on branch retinal artery occlusion was evaluated. METHODS: A fundus contact lens was used to focus the Nd: YAG laser on the embolus within the retinal arteriole. 0.8 to 0.9 mJ of laser pulse was delivered directly to the embolus. Fundus photographs were taken before and immediately after the treatment. Follow-up time ranged from 2 weeks to 4 months, average about 7 weeks. Seven cases received the treatment, including 5 male and 2 female patients. Age of those cases ranged from 49 to 73, average 61 years. The duration of the disease ranged from 1 to 60 days, average 13 days. RESULTS: Before treatment, visual acuity ranged from 0.06 to 0.8. Embolus can be detected in all the 7 cases. After treatment, all the cases showed immediate recovery of blood flow in the occluded arteriole both in fundus examination and fundus fluorescein angiography. The vision in the patients was improved in the follow-up. Visual acuity ranged from 0.2 approximately 1.0. In most cases, visual field defect still existed in the ischemic area. Complications included local retinal hemorrhages in some cases and vitreous hemorrhage, but those hemorrhages were gradually absorbed and did not affect the final visual prognosis. CONCLUSIONS: Nd: YAG laser embolysis for branch retinal artery occlusion is an effective treatment and the treatment is relatively safe.