No abstract

BackgroundProstate cancer (PC) is the second leading cause of cancer-related deaths among men. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) performed as an oncogene in multiple cancers including PC. However, the molecular mechanisms of MALAT1 implicated in PC progression have not been thoroughly elaborated.Materials and methodsReverse transcription-quantitative polymerase chain reaction assay was used to detect the expressions of MALAT1 and microRNA-1 (miR-1). Protein levels of cleaved poly (ADP-ribose) polymerase, cleaved caspase-3, BAX, bcl-2, and KRAS were determined using a western blot assay. Cell proliferation was assessed by colony formation and MTS assays. Cell migration capacity was examined by transwell migration assay (Corning Incorporated, Corning, NY, USA). Apoptosis rate was measured by flow cytometry via double staining of annexin V-FITC and propidium iodide. Luciferase and RNA immunoprecipitation assays were employed to explore the relationship among miR-1, MALAT1, and KRAS.ResultsMALAT1 expression was upregulated and miR-1 expression was downregulated in PC tissues and cell lines. MALAT1 knockdown inhibited cell proliferation and migration, and promoted cell apoptosis in androgen receptor-negative DU145 and PC3 cells. Molecular mechanism explorations disclosed that MALAT1 acted as a molecular sponge of miR-1 in DU145 cells. Moreover, miR-1 downregulation partly abrogated MALAT1 silencing-mediated anti-proliferative, antimigratory, and proapoptotic effects in DU145 and PC3 cells. Further investigation revealed that KRAS was a target of miR-1 in DU145 cells. MALAT1 acted as a competing endogenous RNA of miR-1, resulting in the increase of KRAS expression in DU145 and PC3 cells. Furthermore, miR-1 overexpression hampered proliferation and migration and promoted apoptosis in DU145 and PC3 cells, while these effects were markedly weakened following KRAS upregulation.ConclusionMALAT1 knockdown inhibited proliferation and migration and facilitated apoptosis by upregulating miR-1 and downregulating KRAS in androgen receptor-negative PCa cells, providing a new insight into the molecular basis of MALAT1 and a potential biomarker or therapeutic target for suppressing castration-resistant PC.

Tumor protein D52 (TPD52) is a member of the TPD52-like protein family and plays different roles in various types of malignancies. However, its role in renal cell carcinoma (RCC) is still unclear. In this study, we investigated the role of TPD52 in RCC. The mechanism of TPD52 in RCC was also investigated. Our data demonstrated that the expression levels of TPD52 in both mRNA and protein were significantly decreased in RCC cells. Overexpression of TPD52 inhibited proliferation, migration, and invasion with decreased epithelial-mesenchymal transition (EMT) phenotype in RCC cells, as well as attenuated tumor growth in renal cancer xenografts. Mechanistically, overexpression of TPD52 significantly inhibited downregulated phosphorylation levels of PI3K and Akt in RCC cells. In conclusion, the present study demonstrated that TPD52 inhibited growth and metastasis of RCC, at least in part, by suppressing the PI3K/Akt signaling pathway. Therefore, these findings suggest that TPD52 may be a promising therapeutic target for the treatment of human RCC.

Exogenous H2S may promote cell proliferation and invasion by upregulating the expression level of MMP2 and MMP9 in human bladder cancer EJ cells.

Background LncRNA EMX2OS (EMX2 opposite strand/antisense RNA) is notably downregulated in prostate cancer (PCa) tissues and may be regarded as a potential molecular biomarker for diagnosis and prognosis. However, its exact role in regulating the development of PCa is obscure. Methods The EMX2OS expression was assessed in PCa tissues, paracancer tissues, PCa cells and normal prostate epithelial cells by qPCR. Gain- and loss-of-function experiments were performed to investigate the role of EMX2OS and FUS in cGMP-PKG (cyclic guanosine monophosphate-dependent protein kinase)-mediated proliferation, invasion, and migration in human PCa cell lines DU145 and PC3. Then, the interaction of transcription factor 12 (TCF12) with EMX2OS promoter was confirmed by using the dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RNA binding protein immunoprecipitation and RNA pull-down assays were used to verify the interaction between EMX2OS and FUS protein. Finally, the role of EMX2OS and FUS in tumor growth in vivo was validated in a xenograft nude mouse model. Results TCF12 and EMX2OS were both downregulated in PCa tissues and cells, and they negatively regulated cell proliferation, migration and invasion, and activated cGMP-PKG pathway in DU145 and PC3 cells. TCF12 was a transcription factor of EMX2OS. TCF12 and EMX2OS overexpression both down-regulated cell proliferation, migration and invasion, and activated cGMP-PKG pathway in DU145 and PC3 cells. Furthermore, EMX2OS directly bound with FUS protein and had a synergy effect with FUS protein on cGMP-PKG-mediated cell functions, which could be suppressed by (D)-DT-2 (a cGMP-PKG inhibitor). In addition, the overexpression of FUS or EMX2OS individually markedly decreased the volume and weight of tumors in vivo, and co-overexpression of them further inhibited tumor growth. Conclusion EMX2OS, transcriptionally regulated by TCF12, played a synergy role with FUS protein in regulating the proliferation, migration and invasion of PCa cells by activating the cGMP-PKG pathway.