miRNAs play a key role in the carcinogenesis of many cancers, including bladder cancer. In the current study, the role of miR-5195-3p, a quite recently discovered and poorly studied miRNA, in the proliferation and invasion of human bladder cancer cells was investigated. Our data displayed that, compared with healthy volunteers (control) and SU-HUC-1 normal human bladder epithelial cells, miR-5195-3p was sharply downregulated in bladder cancer patients and five human bladder cancer cell lines. The oligo miR-5195-3p mimic or miR-5195-3p antagomir was subsequently transfected into both T24 and BIU-87 bladder cancer cell lines. The miR-5195-3p mimic robustly increased the miR-5195-3p expression level and distinctly reduced the proliferation and invasion of T24 and BIU-87 cells. In contrast, the miR-5195-3p antagomir had an opposite effect on miR-5195-3p expression, cell proliferation, and invasion. Our data from bioinformatic and luciferase reporter gene assays identified that miR-5195-3p targeted the mRNA 3'-UTR of Krüppel-like factor 5 (KLF5), which is a proven proto-oncogene in bladder cancer. miR-5195-3p sharply reduced KLF5 expression and suppressed the expression or activation of its several downstream genes that are kinases improving cell survival or promoting cell cycle regulators, including ERK1/2, VEGFA, and cyclin D1. In conclusion, miR-5195-3p suppressed proliferation and invasion of human bladder cancer cells via suppression of KLF5.
The identification of markers for disease diagnostic, prognostic, or predictive purposes will have a great effect in improving patient management. Proteomic-based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on four patients including clear cell renal cell carcinoma (ccRCC) and paired adjacent non-cancerous renal tissues using label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. Among 3,061 identified non-redundant proteins, we found that 210 proteins were differentially expressed (83 overexpressed and 127 underexpressed) in ccRCC tissue when compared with normal kidney tissues. Two most significantly dysregulated proteins (PCK1 and SNRPF) were chosen to be confirmed by western blotting. Pathway analysis of 210 differentially expressed proteins showed that dysregulated proteins are related to many cancer-related biological processes such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. Online survival analysis indicated the prognostic value of these dysregulated proteins. In conclusion, we identified some potential diagnostic biomarkers for ccRCC and an in-depth understanding of their involved biological pathways may help pave the way to discover new therapeutic strategies for ccRCC.
This is the first study to emphasize the expression of miR-451 on regulating multidrug resistance (MDR) in renal cell carcinoma (RCC). Our study found that miR-451 regulates the drug resistance of RCC by targeting ATF-2, which might be critical for overcoming MDR in RCC patients. This study not only provides solid theory foundation for the clinical therapy, but also offers unique insights for the further RCC research. Furthermore, the study helps us to understand the mechanism of MDR, which was crucial for identifying the chemoresistance on several related tumors. AbstractRenal cell carcinoma (RCC) is a malignant tumor, which severely threatens human's life, moreover, the multi-drug resistance (MDR) under RCC undoubtedly strengthen the difficulties in the treatment. MiR-451 has been considered to play an important role in regulation of MDR in several cancers, but the role of it in MDR of RCC has not been explored. This study aims to explore the mechanism of miR-451 as a target to regulate chemotherapy resistance, which is crucial for further exploring novel therapy for RCC. Two human cell lines (ACHN and GRC-1) were performed in this study and adriamycin (ADM) was used to construct MDR cell lines. qRT-PCR was used to determine the mRNA expression of miR-451 and ATF-2. Weston blot was used to determine protein expression. MTT assay and flow cytometry were used for assessing cell viability and apoptosis, individually. Luciferase reporter assay was used to detect the targeting of miR-451 and ATF-2. Results presented that the expression of miR-451 was higher in low MDR cell line (ACHN) comparing with the high MDR cell line (GRC-1), while the expression of ATF-2 revealed an opposite results. MiR-451 targeted ATF-2 and regulated its expression. Overexpression of miR-451 strengthened drug resistance, decreased cell viability, and increased cell apoptosis of GRC-1 pretreated by ADM, while overexpressed ATF-2 reversed the effect induced by miR-451 overexpression. Then miR-451 knockdown improved drug susceptibility, decreased cell apoptosis, and increased cell viability of ACHN induced by ADM, however, ATF-2 suppression reversed the low rate of cell apoptosis and high rate of cell viability induced by miR-451 knockdown. Our results revealed that miR-451 regulates the drug resistance of RCC by targeting ATF-2 gene, which might be critical for overcoming MDR in RCC patients.
Background: LncRNA PCAT29 has been reported to play a role in the development of cancer; the role of FLOT1 in renal carcinoma has been also identified. This study aimed at exploring the interaction between them and their influence on the progression of renal carcinoma. Methods: The expression levels of lncRNA PCAT29 and the FLOT1 protein in tissues were determined separately using qRT-PCR and western blot, respectively. The endogenous expression of genes was modulated by recombinant plasmid and cell transfection. The cell viability, invasion, and migration were detected by MTT assay, transwell assay, and wound-healing cell migration assay, respectively. Any binding and interactions between the RNA and the proteins were determined with RNA immunoprecipitation and RNA pull-down assays. A nude mouse model for renal carcinoma was established for the in vivo expression of PCAT29. Results: In renal carcinoma tissues, the expression of lncRNA PCAT29 was down-regulated while that of FLOT1 was up-regulated. PCAT29 negatively regulated FLOT1, and the overexpression of PCAT29 inhibited the cell proliferation viability, invasion, and migration of renal carcinoma by down-regulating FLOT1. The in vivo expression of PCAT29 inhibited tumor growth in a mouse model of renal carcinoma. Conclusion: LncRNA PCAT29 inhibited the cell proliferation viability, invasion, and migration in renal carcinoma by down-regulating FLOT1, thereby suppressing tumor growth.
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