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The aetiology of bone metastasis in prostate cancer (PCa) remains unclear. This study aims to identify hub genes involved in this process. We utilized machine learning, GO, KEGG, GSEA, Single-cell analysis, ROC methods to identify hub genes for bone metastasis in PCa using the TCGA and GEO databases. Potential drugs targeting these genes were identified. We validated these results using 16 specimens from patients with PCa and analysed the relationship between the hub genes and clinical features. The impact of APOC1 on PCa was assessed through in vitro experiments. Seven hub genes with AUC values of 0.727-0.926 were identified. APOC1, CFH, NUSAP1 and LGALS1 were highly expressed in bone metastasis tissues, while NR4A2, ADRB2 and ZNF331 exhibited an opposite trend. Immunohistochemistry further confirmed these results. The oxidative phosphorylation pathway was significantly enriched by the identified genes. Aflatoxin B1, benzo(a)pyrene, cyclosporine were identified as potential drugs. APOC1 expression was correlated with clinical features of PCa metastasis. Silencing APOC1 significantly inhibited PCa cell proliferation, clonality, and migration in vitro. This study identified 7 hub genes that potentially facilitate bone metastasis in PCa through mitochondrial metabolic reprogramming. APOC1 emerged as a promising therapeutic target and prognostic marker for PCa with bone metastasis.
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Neoplasias Ósseas , Proliferação de Células , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Humanos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Biologia Computacional/métodos , Proliferação de Células/genética , Linhagem Celular Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , PrognósticoRESUMO
Gypsum Fibrosum, as a classic heat-clearing medicine, is widely used in the clinical practice of traditional Chinese medicine(TCM). However, debates exist about the material basis and mechanism of its efficacy. Therefore, this paper reviewed the recent research progress in the heat-clearing effect and mechanism of Gypsum Fibrosum and discussed the material basis for the heat-clearing effect of this medicine. Ca~(2+) may inhibit the upward movement of temperature set point by regulating the Na~+/Ca~(2+) level in the heat-regulating center. Moreover, trace elements may inhibit the rise of body temperature by regulating the immune system, promoting the absorption of Ca~(2+), and affecting the synthesis of prostaglandin E2(PGE2). This review aims to enrich the knowledge about the mechanism of Gypsum Fibrosum in clearing heat and provides a scientific basis for the clinical application and further development of Gypsum Fibrosum.
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Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Sulfato de Cálcio/farmacologia , Temperatura Alta , Medicina Tradicional ChinesaRESUMO
Circular RNA (circRNA), a type of noncoding RNAs, has been demonstrated to act vital roles in tumorigenesis and cancer deterioration. Although tumor-associated macrophages are involved in tumor malignancy, the interactions between circRNAs and tumor-associated macrophages in prostate cancer (PCa) remain unclear. In the present study, we found that hsa_circ_0094606 (subsequently named circ_0094606) could promote proliferation, epithelial-mesenchymal transition (EMT) as well as migration of PCa cells through cell viability and migration assays and the determination of EMT markers. Mass spectrometry analysis after RNA pull-down experiment identified that circ_0094606 bound to protein arginine methyltransferase 1 (PRMT1) in PCa cells, and further functional assays revealed that circ_0094606 promoted the malignant progression of PCa by binding to PRMT1. Moreover, co-immunoprecipitation (Co-IP), glutathione-S-transferase (GST) pull-down and immunofluorescence showed that PRMT1 mediated arginine methylation of ILF3 to stabilize the protein. Bioinformatics analysis combined with data from RNA-binding protein immunoprecipitation and RNA pull-down suggested that ILF3 could stabilize IL-8 mRNA, which promoted the M2 polarization in coculture study. Finally, in vivo experiments showed that circ_0094606 subserve PCa growth and promoted the M2 polarization of macrophages through the PRMT1/ILF3/IL-8 regulation pathway, supporting circ_0094606 as a potential novel effective target for PCa treatment.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Metilação , Arginina/genética , Arginina/metabolismo , Interleucina-8/genética , RNA/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Metiltransferases/genética , Neoplasias da Próstata/genética , Macrófagos/metabolismo , MicroRNAs/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Circular RNAs (circRNAs) are a type of non-coding RNA that plays a vital role in biology. circRNAs appear to have a role in the development and progression of several malignancies, according to research. However, circRNAs that regulate prostate cancer (PCa) progression are still largely unknown and deserve further exploration. The aim of this study was to investigate the effect of hsa_circ_0070512 on the function and mechanism of PCa. hsa_circ_0070512 was increased in PCa tissues and cells and was mostly found in the cytoplasm of PCa cells. Overexpression of hsa_circ_0070512 considerably increased PCa cell proliferation and migration, whereas silencing of hsa_circ_0070512 greatly decreased PCa cell proliferation and migration. Mechanistically, we show that hsa_circ_0070512 acts as a "molecular sponge" for miR-338-3p and that the miR-338-3p mimics partially block the pro-tumor effects of hsa_circ_0070512. RNA sequencing analysis of PC3 cells stably overexpressing hsa_circ_0070512 revealed that hedgehog was downstream of the signaling pathways of hsa_circ_0070512 and miR-338-3p. Our results implied that hsa_circ_0070512 regulated the hedgehog signaling pathways through miR-338-3p to enhance PCa growth and migration, providing a new diagnostic and therapeutic target for PCa.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias da Próstata/genética , Transdução de Sinais/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: The epidemiological investigation of different cancer types in the global population has reported a decreased risk of bladder cancer (BLCA) in Parkinson's diseases (PD). SNCA a critical gene in PD pathology have been reported involved in tumorigenesis recently. However, the role of SNCA in BLCA remains unclear. This study aimed to explore the potential value of SNCA as a prognostic diagnostic molecular biomarker in BLCA. METHODS: In this study, we explored the expression pattern, prognostic value and promoter methylation level of SNCA in BLCA by GEPIA2, UALCAN, TCGA, GENT2, GEO and c-BioPortal database. Then, we used LinkedOmics database to obtain the co-expression genes of SNCA for further study by WGCNA. We further investigated the correlations between SNCA expression and six main types of immune cell infiltrations and immune signatures by TIMER. Finally, BLCA cell lines treated with 5-Aza-CdR were used to explore the correlation between increased methylation and downregulated mRNA expression. RESULTS: SNCA was downregulated in tumor tissues in TCGA-BLCA, GENT2 and GEO, which was validated in our cohort by qRT-PCR and immunohistochemistry. SNCA was confirmed as an independent predictor of poor overall survival (OS). LinkedOmics analysis suggested that SNCA regulates cell adhesion molecules, cytokine-cytokine receptor interaction, and complement and coagulation cascades. Twenty-two co-expression gene modules were constructed by WGCNA, and most of them were significantly associated with OS and disease-free survival (DFS). Six key genes (CNTN1, DACT3, MYLK1, PDE2A, RBM24, and ST6GALNAC3) screened also significantly correlated with prognosis. There were significant correlations between SNCA expression and immune infiltrations, especially T cell, suggesting that immune infiltration was one of the reasons for the influence of SNCA on prognosis in BLCA. Analysis by ULACAN and c-BioPortal showed that the promoter methylation of SNCA negatively correlated with its mRNA level. Furthermore, BLCA cell treatment with 5-Aza-CdR revealed that SNCA expression levels were upregulated with decreased methylation. CONCLUSION: Our research showed that SNCA was downregulated in BLCA and negatively correlation with DNA methylation. High SNCA expression was confirmed as an independent risk for prognosis. SNCA probably plays an important role in the infiltration of immune cells, especially with T cells. Thus, SNCA may be a promising prognostic biomarker in BLCA patients.
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Neoplasias da Bexiga Urinária , alfa-Sinucleína , Metilação de DNA , Redes Reguladoras de Genes , Humanos , Prognóstico , Regiões Promotoras Genéticas , Proteínas de Ligação a RNA/genética , Neoplasias da Bexiga Urinária/patologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND: In order to investigate how valsartan-the angiotensin II 1 receptor (AT1R) antagonist-affects the expressions of AT1R antigen, matrix metalloproteinases (MMPs) -2 and -9 in carcinoma of urinary bladder (CUB) cell lines with different invasive abilities. METHODS: Three cell lines, EJ-M3, EJ, and BIU-87, with different invasive abilities were cultured and treated with valsartan. Cell proliferation states were determined by the methyl thiazolyl tetrazolium (MTT) method. The expressions at protein level and gene level were determined by Western blot and real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR), respectively. The invasive abilities and migratory abilities of the three cell lines were determined by Transwell in vitro cell invasion assay and wound healing assay, respectively. RESULTS: MTT results show that valsartan can inhibit the proliferation of CUB cells, and the inhibition effect is enhanced with the increase of concentration. CONCLUSIONS: AngII promotes the MMP2 and MMP9 expressions (both protein and gene levels) in CUB cells through AT1R, but their expressions can be effectively inhibited by valsartan, the AngII inhibitor. AngII inhibitor may become a novel drug that can inhibit CUB metastasis and prolong the survival of CUB patients.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Receptor Tipo 1 de Angiotensina/análise , Neoplasias da Bexiga Urinária/tratamento farmacológico , Valsartana/farmacologia , Linhagem Celular Tumoral , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica , RNA Mensageiro/análise , Receptor Tipo 1 de Angiotensina/genética , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: This work aimed to evaluate the efficacy of virtual reality (VR) technology in neurosurgical anatomy through a comparison of the virtual 3D microanatomy of the suboccipital vertebral arteries and their bony structures as part of the resection of tumors in the craniovertebral junction (CVJ) of 20 patients compared to the actual microanatomy of the vertebral arteries of 15 cadaveric headsets. MATERIAL AND METHODS: The study was conducted with 2 groups of data: a VR group composed of 20 clinical cases and a physical body group (PB group) composed of 15 cadaveric headsets. In the VR group, the dissection and measurements of the vertebral arteries were simulated on a Dextroscope. In the PB group, the vertebral arteries in the cadaver heads were examined under a microscope and anatomical measurements of VA and bony structures were performed. The length and course of the vertebral arteries and its surrounding bony structures in each group were compared. RESULTS: The distances from the inferior part of the transverse process foramen (TPF) of C1 to the inferior part of TPF of C2 were 17.68±2.86 mm and 18.4±1.82 mm in the PB and VR groups, respectively. The distances between the middle point of the posterior arch of the atlas and the medial intersection of VA on the groove were 17.35±2.23 mm in the PB group and 18.13±2.58 mm in the VR group. The distances between the middle line and the entrance of VA to the lower rim of TPF of Atlas were 28.64±2.67 mm in PB group and 29.23±2.89 mm in VR group. The diameters of the vertebral artery (VA) at the end of the groove and foramen of C2 transverse process were 4.02±046 mm and 4.25±0.51 mm, respectively, in the PB group and 3.54±0.44 mm and 4.47±0.62 mm, respectively, in VR group. The distances between the VA lumen center and midline of the foramen magnum at the level of dural penetration was 10.4±1.13 mm in the PB group and 11.5±1.34 mm in the VR group (P>0.05). CONCLUSIONS: VR technology can accurately simulate the anatomical features of the suboccipital vertebral arteries and their bony structures, which facilitates the planning of individual surgeries in the CVJ.
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Procedimentos Neurocirúrgicos/métodos , Lobo Occipital/irrigação sanguínea , Coluna Vertebral/anatomia & histologia , Interface Usuário-Computador , Artéria Vertebral/anatomia & histologia , Adulto , HumanosRESUMO
RATIONALE: TFEB-associated renal cell carcinoma is very rare and belongs to the microphthalmia - associated transcription family translocation renal cell carcinoma. PATIENT CONCERNS: Hospitalized for fever, a 29-year-old male patient had a left kidney lesion without any additional discomfort. DIAGNOSES: Histopathological and immunohistochemical results were corresponding with TFEB renall cell carcinoma features. INTERVENTIONS: Surgical resection of the tumor was performed. OUTCOMES: After 8 months of follow-up, no tumor recurrence was observed. LESSONS: TFEB-associated renal cell carcinoma is rare. The diagnosis is explicit. However, the optimal treatment needs to be further explored.
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Carcinoma de Células Renais , Neoplasias Renais , Masculino , Humanos , Adulto , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/genética , Neoplasias Renais/patologia , Translocação Genética , Biomarcadores Tumorais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Recidiva Local de NeoplasiaRESUMO
Bladder cancer (BC) is one of the most common malignancies involving the urinary system. Our previous study demonstrated that cobra venom membrane toxin 12 (MT-12) could effectively inhibit BC cell growth and metastasis and induce apoptosis. However, the specific molecular mechanism remains unknown. In this study, we explored whether MT-12 inhibits BC cell proliferation by inducing autophagy cell death through mitochondrial dysfunction. As a result, MT-12 inhibited proliferation and colony formation in RT4 and T24 cells. In the BC xenograft mouse model, autophagy inhibitor 3-MA alleviated the inhibitory effect of MT-12 on tumor growth. In addition, immunostaining revealed downregulated autophagy in MT-12-treated RT4 and T24 cells. We also found that MT-12 led to dysfunctional mitochondria with decreased mitochondrial membrane potential, mtDNA abundance, and increased ROS production, ultimately inducing autophagic apoptosis via the ROS/JNK/P53 pathway. MT-12 inhibits BC proliferation in vitro and in vivo by enhancing autophagy. MT-12 induces mitochondrial dysfunction and decreases autophagy, leading to increased ROS production, which in turn activates the JNK/p53 pathway, leading to BC apoptosis.
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Prostate cancer (PCa) is one of the most prevalent cancers of the urinary system. In previous research, Kinesin family member 2C (KIF2C), as an oncogene, has been demonstrated to have a key role in the incidence and progression of different cancers. However, KIF2C has not been reported in PCa. We combined data from different databases, including The Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and the Genomics of Drug Sensitivity in Cancer database, to explore the potential oncogenic role of KIF2C in PCa through a series of bioinformatics approaches, including analysis of the association between KIF2C and prognosis, clinicopathological features, gene mutations, DNA methylation, immune cell infiltration, and drug resistance. The results showed that KIF2C was significantly up-regulated in PCa. High KIF2C expression was associated with age, pathological stage, lymph node metastases, prostate-specific antigen (PSA), and Gleason score and significantly predicted an unfavorable prognosis in PCa patients. Results from Gene Set Enrichment Analysis (GSEA) suggested that KIF2C was involved in the cell cycle and immune response. KIF2C DNA methylation was reduced in PCa and was inversely linked with KIF2C expression. KIF2C was shown to have a strong relationship with the tumor microenvironment (TME), infiltrating cells, and immune checkpoint genes. Furthermore, high KIF2C expression was significantly resistant to a variety of MAPK signaling pathway-related inhibitors. Our study reveals that KIF2C may be a possible predictive biomarker for assessing prognosis in PCa patients with immune infiltration.
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Neoplasias da Próstata , Transcriptoma , Análise de Dados , Perfilação da Expressão Gênica/métodos , Humanos , Cinesinas/genética , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente Tumoral/genéticaRESUMO
Alpha-synuclein (α-syn), encoded by the SNCA gene, is a major participant in the pathophysiology of Parkinson's disease (PD). Its functions have been reported to be related to apoptosis induction, the elevation of oxidative stress, mitochondrial homeostasis, cell-cycle aberrations, and DNA-related interactions. Evidence obtained in recent studies suggests a possible link between α-syn and cancer development. Bladder cancer (BCa) is the second most common genitourinary malignancy, with the population of survivors of BCa increasing worldwide. In this study, we show that α-syn expression was significantly downregulated in BCa. In vitro and in vivo experiments showed that α-syn could significantly inhibit BCa cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages. Further experiments showed that overexpression of α-syn delivered by adeno-associated viruses (AAVs) exerted inhibitory effects on the growth of BCa tumors. These findings indicate that αα-syn is a functional tumor suppressor that can inhibit the proliferation of BCa cells by activating the p53/p21 signaling pathway. Our present study provides insights into the roles of α-syn in BCa and suggests that α-syn may be a novel therapeutic target for the treatment of BCa.
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Neoplasias da Bexiga Urinária , alfa-Sinucleína , Dependovirus/genética , Dependovirus/metabolismo , Humanos , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/patologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND: Multiomics data analysis based on high-throughput sequencing technology has become a hotspot in tumor investigation. The present study aimed to explore prognostic biomarkers via investigating DNA copy number variation (CNV) and methylation variation (MET) data in prostate cancer. METHODS: We obtained the messenger RNA (mRNA) expression, CNV, and methylated data of prostate adenocarcinoma (PRAD) samples via The Cancer Genome Atlas (TCGA)-PRAD cohort. We calculated and assessed the associations between CNV and RNA sequencing (RNA-seq), and between MET and RNA-seq via Pearson correlation coefficients. We then used the "iCluster" package to perform multigroup cluster analysis with CNVcor gene CNV data, METcor gene methylation data, and CNVcor and METcor gene mRNA data. The univariate Cox analysis was used to screen significant hub genes, and multivariate Cox analysis was used to construct risk a model. The nomogram was constructed based on "rms" package, and the immune infiltrating patterns were compared between high- and low-risk groups. RESULTS: A total of 477 PRAD samples with complete CNV, methylation, mRNA, and matched clinical information were included in our study. A list of 10,073 CNVcor genes and 9841 METcor genes were confirmed with a significance level of P<0.01. We found that CNVcor is more likely to appear on chromosome (chr)8, chr17, and chr10, while METcor is more likely to appear on chr1, chr19, and chr17. Based on the core genes, we finally classified the samples into 4 subtypes, incorporating iC1 (iCluster) (92 samples), iC2 (79 samples), iC3 (165 samples), and iC4 (141 samples). Furthermore, we constructed the prognostic model for PRAD based on the 5 genes (IER3, AOX1, PRKCDBP, UBD, and FBLN5). Nomograms incorporating risk score and other clinical variables were further constructed, and these nomograms exhibited superior predictive ability. We further compared the differential immune infiltrating patterns in 2 risk groups and found significantly low levels of infiltrating cluster of differentiation (CD)8+ T cells in high-risk samples. CONCLUSIONS: Our study integrated the multi-omics data to elucidate the molecular features of PRAD and pivotal genes for predicting prognosis.
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We present a complicated case of spontaneous cerebrospinal otorrhea, which had not been cured despite undergoing 5 surgical interventions in the past. The disability to identify the location of the fistula was the main crux of the past failures. On this occasion, stereoscopic virtual reality presurgical planning was applied to identify the exact location of the fistula and a surgical simulation was performed, and was later confirmed during the actual operation. Interactive manipulation in a stereoscopic virtual environment makes the decision making process easier in the treatment of cerebrospinal otorrhea.
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Otorreia de Líquido Cefalorraquidiano/cirurgia , Simulação por Computador , Cuidados Pré-Operatórios , Interface Usuário-Computador , Adulto , Otorreia de Líquido Cefalorraquidiano/patologia , Otorreia de Líquido Cefalorraquidiano/fisiopatologia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
Paris forrestii is a unique plant found in Tibet and Yunnan, China, and total saponins from Paris forrestii (PCT3) contain anticancer steroid glycosides. RNA expression plays an important role in various biological processes. However, the cytotoxicity effects and mechanisms of PCT3 in relation to prostate cancer (PCa) cells have not yet been reported. In the present study, the antitumor activity of PCT3 on PCa cells was evaluated. PCT3 displayed potent anticancer effects toward PCa cells that were similar to the effects of pure saponins from P. forrestii, but PCT3 had less activity in suppressing the prostate epithelial cell line RWPE. Furthermore, using CCK-8 assays, Edu incorporation, colony formation assays, Annexin V/PI assays and western blotting, we found that treatment with 4⯵g/mL PCT3 significantly decreased proliferation and induced apoptosis in PCa cells. Using wound healing and transwell assays, we demonstrated that treatment with 2⯵g/mL PCT3 significantly suppressed the migration and invasion of PCa cells. To explore the molecular mechanisms behind the anticancer effect of PCT3, PCT3 (5⯵g/mL) treated and untreated PCa cells (LNCAP and PC3 cell lines) were analyzed using transcriptomics. Taking the commonly differentially expressed genes (log2FCâ¯>â¯0.585) in both cell lines, 41 mRNAs and 5 lncRNAs were eventually identified. Bioinformatics analysis (GO and KEGG analyses) revealed that some genes involved in classical cell proliferation and apoptosis pathways were aberrantly expressed after PCT3 treatment of PCa cells. By using q-PCR, the expression levels of NEAT1, MALAT1, TIPIN, LYAR, IQGAP3, GINS2, and ZGRF1 were validated as consistent with microarray data, suggesting that these genes might participate in the PCT3 anticancer effect. The present study suggests that PCT3 exhibits an anticancer effect on PCa and reveals some crucial lncRNAs and mRNAs that are involved in the anticancer mechanisms of PCT3 on Pca.