Endocrine therapy for prostate cancer (PCa) mainly inhibits androgen receptor (AR) signaling, due to increased androgen synthesis and AR changes, PCa evolved into castration-resistant prostate cancer (CRPC). The function of Family With Sequence Similarity 64 Member A (FAM64A) and its association with prostate cancer has not been reported. In our research, we first reported that FAM64A is up-regulated and positively associated with poor prognosis of patients with prostate cancer (PCa) by TCGA database and immunohistochemistry staining. Moreover, knockdown of FAM64A significantly suppressed the proliferation, migration, invasion, and cell cycle of PCa cells in vitro. Mechanistically, FAM64A expression was increased by dihydrotestosterone (DHT) through direct binding of AR to FAM64A promoter, and notably promoted the proliferation, migration, invasion, and cell cycle of androgen-dependent cell line of PCa. In addition, abnormal expression of FAM64A affects the immune and interferon signaling pathway of PCa cells. In conclusion, FAM64A was up-regulated by AR through directly binding to its specific promoter region to promote the development of PCa, and was associated with the immune mechanism and interferon signaling pathway, which provided a better understanding and a new potential for treating PCa.

Objective To explore the hypermethylated long non-coding (lnc)RNAs involved in bladder carcinogenesis and prognosis. Methods Reduced representation bisulfite sequencing and RNA sequencing were performed on five paired tumor and adjacent normal tissue samples from bladder cancer patients. The differentially methylated regions around transcription start sites and differentially expressed genes, including lncRNAs, were analyzed. Correlations between DNA methylation modifications and the expression of lncRNAs were examined. Survival analysis was surveyed on the GEPIA web server. Results We identified 19,560 hypomethylated and 68,781 hypermethylated differentially methylated regions around transcription start sites in bladder cancer tissues. In total, 2321 differentially expressed genes were found in bladder tumors, among which, 367 were upregulated and 1954 were downregulated. There were 141 downregulated genes involving eight lncRNAs that were consistently hypermethylated, while 24 upregulated genes were consistently hypomethylated. Survival analysis demonstrated that hypermethylation of lncRNAs LINC00683 and MSC-AS1 were associated with poor overall survival in bladder cancer patients. Conclusion Some lncRNAs are controlled by DNA methylation in bladder cancer and they might be important factors in bladder carcinogenesis. Hypermethylated lncRNAs including LINC00683 and MSC-AS1 have the potential to be prognostic biomarkers for bladder cancer.

Background: SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1), a component of the SWI/SNF complex, is thought to be an oncogene in several kinds of cancer.Materials and methods: The potential interaction between SMARCC1 and KPNA2 was inquired by Spearman’s correlation analysis, immunofluorescence staining and co-immunoprecipitation (Co-IP) assays. The immunohistochemistry staining, RT-PCR and western blot assay were taken for determining the expression levels of SMARCC1. And CCK-8, transwell assay, cell apoptosis assay, cell cycle analysis and subcutaneous tumor model were conducted to explore the role of SMARCC1 in carcinogenesis of bladder cancer.Results: In our experiments, Spearman’s correlation analysis, immunofluorescence staining and co-immunoprecipitation (Co-IP) assays showed that SMARCC1 interacted with KPNA2, and after knockdown of KPNA2, Nup50 and Nup153, the nuclear content of SMARCC1 decreased while the amount of SMARCC1 protein remaining in the cytoplasm increased, indicating that SMARCC1 could be transported into the nucleus via KPNA2 and thus acted as an oncogene. We found that both the mRNA and protein expression levels of SMARCC1 were increased in bladder cancer, and increased SMARCC1 expression was significantly associated with a higher T stage and poorer prognosis in bladder cancer patients. Knockdown of SMARCC1 slowed the growth of the two tested cell lines and clearly arrested the cell cycle at the G0/G1 phase checkpoint. Moreover, the migratory ability was significantly decreased and the number of apoptotic cells was increased.Conclusion: On the whole, our results demonstrate KPNA2, Nup50 and Nup153 regulate the process of SMARCC1 nuclear translocation in BC. SMARCC1 may be a competent candidate as a diagnostic and therapeutic target for BC. Further studies are required to research the mechanism and assess the role of SMARCC1 in vivo.

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