Identification of prostate cancer bone metastasis related genes and potential therapy targets by bioinformatics and in vitro experiments.

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.

Comprehensive scRNA-seq analysis to identify new markers of M2 macrophages for predicting the prognosis of prostate cancer.

BACKGROUND: Prostate cancer (PCa) has become the highest incidence of malignant tumor among men in the world. Tumor microenvironment (TME) is necessary for tumor growth. M2 macrophages play an important role in many solid tumors. This research aimed at the role of M2 macrophages' prognosis value in PCa. METHODS: Single-cell RNA-seq (scRNA-seq) data and mRNA expression data were obtained from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA). Quality control, normalization, reduction, clustering, and cell annotation of scRNA-seq data were preformed using the Seruat package. The sub-populations of the tumor-associated macrophages (TAMs) were analysis and the marker genes of M2 macrophage were selected. Differentially expressed genes (DEGs) in PCa were identified using limma and the immune infiltration was detected using CIBERSORTx. Then, a weighted correlation network analysis (WGCNA) was constructed to identify the M2 macrophage-related modules and genes. Integration of the marker genes of M2 macrophage from scRNA-seq data analysis and hub genes from WGCNA to select the prognostic gene signature based on Univariate and LASSO regression analysis. The risk score was calculated, and the DEGs, biological function, immune characteristics related to risk score were explored. And a predictive nomogram was constructed. CCK8, Transwell, and wound healing were used to verify cell phenotype changes after co-cultured. RESULTS: A total of 2431 marker genes of M2 macrophage and 650 hub M2 macrophage-related genes were selected based on scRNA-seq data and WGCNA. Then, 113 M2 macrophage-related genes were obtained by overlapping the scRNA-seq data and WGCNA results. Nine M2 macrophage-related genes (SMOC2, PLPP1, HES1, STMN1, GPR160, ABCG1, MAZ, MYC, and EPCAM) were screened as prognostic gene signatures. M2 risk score was calculated, the DEGs, Immune score, stromal score, ESTIMATE score, tumor purity, and immune cell infiltration, immune checkpoint expression, and responses of immunotherapy and chemotherapy were identified. And a predictive nomogram was constructed. CCK8, Transwell invasion, and wound healing further verified that M2 macrophages promoted the proliferation, invasion, and migration of PCa (p < 0.05). CONCLUSIONS: We uncovered that M2 macrophages and relevant genes played key roles in promoting the occurrence, development, and metastases of PCa and played as convincing predictors in PCa.

TFEB-associated renal cell carcinoma: A case report and literature review.

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.

MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction.

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.

Adeno-associated virus-delivered alpha synuclein inhibits bladder cancer growth via the p53/p21 signaling pathway.

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.