Search

RIP analysis for circPTPRA enrichment in T24T cells transiently transfected with plasmids containing the indicated FLAG-tagged full-length or truncated constructs. b Reducing MYC and FSCN1 mRNA half-life by overexpressing circPTPRA in T24T cells. D. CCK-8 assay was performed to evaluate cell viability in BC cells with stable overexpression or knockout of IGF2BP1. [Extracted from the article]

SOX2, a member of the SRY-related HMG-box (SOX) family, is abnormally expressed in many tumors and associated with cancer stem cell-like properties. Previous reports have shown that SOX2 is a biomarker for cancer stem cells in human bladder cancer (BC), and our most recent study has indicated that the inhibition of SOX2 by anticancer compound ChlA-F attenuates human BC cell invasion. We now investigated the mechanisms through which SOX2 promotes the invasive ability of BC cells. Our studies revealed that SOX2 promoted SKP2 transcription and increased SKP2-accelerated Sp1 protein degradation. As Sp1 is a transcriptionally regulated gene, HUR transcription was thereby attenuated, and, in the absence of HUR, FOXO1 mRNA was degraded fast, which promoted BC cell invasion. In addition, SOX2 promoted BC invasion through the upregulation of nucleolin transcription, which resulted in increased MMP2 mRNA stability and expression. Collectively, our findings show that SOX2 promotes BC invasion through both SKP2-Sp1-HUR-FOXO1 and nucleolin-MMP2 dual axes. [ABSTRACT FROM AUTHOR]

The long non‐coding RNA (lncRNA) SNHG1 has been shown to be implicated in the progression of multiple human carcinomas. Nevertheless, the biological functions and potential mechanism of SNHG1 in bladder cancer (BC) are uncharacterized. In the present study, SNHG1 was found to be substantially up‐regulated in BC tissues and cells and was intimately correlated with the TNM stage, lymphatic invasion, metastasis and recurrence‐free survival in BC patients. Down‐regulation of SNHG1 dramatically attenuated the proliferation, migration and invasion of BC cells, whereas the ectopic overexpression of SNHG1 had the opposite effects in vitro. The in vivo experimental results also indicated that SNHG1 down‐regulation hampered the tumour growth and metastasis of BC cells. Mechanistic investigations revealed that SNHG1 enhances HK2 expression by serving as an endogenous sponge to regulate miR‐143‐3p in the cytoplasm of BC cells. In the nucleus, SNHG1 could interact with EZH2 and regulate the histone methylation of the CDH1 promoter, altering the biological behaviours of BC cells. Overall, these findings elucidate an oncologic role of SNHG1 in BC and provide a new therapeutic strategy against BC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been revealed to play important roles in modulating gene expression and are involved in several pathological processes. However, a large number of the circRNAs in bladder cancer progression remain undetermined. In this study, the expression level of circCDYL was detected by quantitative real-time PCR in bladder cancer tissues. The circCDYL over-expression plasmid was constructed and transfected into bladder cancer cell lines. The cell migration was detected by using transwell migration assay and wound healing assay, and cell cycles were detected by flow cytometry. The relative protein expression was detected by Western blotting. It was found that circCDYL was low expressed in bladder cancer tissues and cell lines. Functionally, over-expression of circCDYL inhibited cell growth and migration. Importantly, over-expression of circCDYL down-regulated the protein level of C-MYC in both EJ and T24T cells, while the mRNA level of C-MYC was not significantly reduced. Furthermore, over-expression of C-MYC could partly reverse the G0/G1 phase cell cycle arrest induced by circCDYL in bladder cancer cells. Our findings suggest that circCDYL functions as a tumor suppressor in bladder cancer by down-regulating the expression of C-MYC, and this circular RNA might be used as a new target for bladder cancer therapy. [ABSTRACT FROM AUTHOR]

Our recent studies demonstrate that X‐linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here, we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N‐butyl‐N‐(4‐hydroxybutyl)‐nitrosamine (BBN)‐treated mice in comparison to bladder tissues from vehicle‐treated mice and human BCs in comparison to the paired adjacent normal bladder tissues. Knockdown of XIAP attenuated RhoGDIβ expression and reduced cancer cell invasion, whereas RhoGDIβ expression was attenuated in BBN‐treated urothelium of RING‐deletion knockin mice. Mechanistically, XIAP stabilized RhoGDIβ mRNA by its positively regulating nucleolin mRNA stability via Erks‐dependent manner. Moreover, ectopic expression of GFP‐RhoGDIβ in T24T(shXIAP) cells restored its lung metastasis in nude mice. Our results demonstrate that XIAP‐regulated Erks/nucleolin/RhoGDIβ axis promoted BC invasion and lung metastasis. [ABSTRACT FROM AUTHOR]

Increasing evidences suggest that circular RNAs (circ RNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circ RNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circ RNAs are significantly dysregulated in human bladder cancer tissues. We further show that circ HIPK3, also named bladder cancer-related circular RNA-2 ( BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over-expression of circ HIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo. Mechanistic studies reveal that circ HIPK3 contains two critical binding sites for the micro RNA miR-558 and can abundantly sponge miR-558 to suppress the expression of heparanase ( HPSE). Taken together, our findings provide evidence that circ RNAs act as 'micro RNA sponges', and suggest a new therapeutic target for the treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was downregulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through interacting with 5'UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as "microRNA sponges", and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4-IT1 predicates poor prognosis and promotes tumor progress in several cancers. However, the underlying mechanism of SPRY4-IT1 in bladder cancer remains unknown. In this study, we found that SPRY4-IT1 knockdown induced inhibition of cell proliferation, cell migration and invasion ability, and caused promotion of apoptosis in bladder cancer both in vitro and in vivo. Mechanistically, knockdown of SPRY4-IT1 increased the expression of miR-101-3p and subsequently inhibited the expression of EZH2 at posttranscriptional level. Importantly, SPRY4-IT1 could directly interact with miR-101-3p and down-regulation of miR-101-3p efficiently reversed the suppression of EZH2 induced by SPRY4-IT1 shRNA. Thus, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p, and played an oncogenic role in bladder cancer progression. Together, our study elucidates the role of LncRNA SPRY4-IT1 as a miRNA sponge in bladder cancer, and sheds new light on LncRNA-directed diagnostics and therapeutics in bladder cancer. [ABSTRACT FROM AUTHOR]

Our study aimed to explore long non-coding RNAs (lncRNAs) contributing to the development of bladder cancer, as well as to identify more critical DEGs and lncRNAs that would characterize low- and high-grade bladder cancer. The microarray data of GSE55433 was downloaded from Gene Expression Omnibus database, including 57 urothelial cancer samples (23 low-grade NMI, 14 high-grade NMI and 20 invasive tumors) and 26 normal controls. The differentially expressed genes (DEGs) and differentially expressed lncRNAs were identified in 3 groups (low-grade NMI vs. normal, high-grade NMI vs. normal and invasive UC vs. normal). Functional enrichment analysis was performed upon the DEGs in different groups. Besides, protein-protein interaction (PPI) network was constructed based on common DEGs and remaining DEGs in each group. Co-expression analysis was performed to identify the co-expressed DEG-lncRNAs pairs. Different number of DEGs and differentially expressed lncRNAs were respectively identified from those 3 groups. NONHSAG013805 (down-regulated) and NONHSAG009271 (down-regulated) were common lncRNAs. NONHSAG013805 was connected with the down-regulated gene EIF3E and NONHSAG009271 was linked to MYL12A (down-regulated). Moreover, NONHSAG034203 (up-regulated) was co-expressed with ADM5 (up-regulated) in low-grade NMI cancer, while the down-regulated NONHSAG045391 was connected with the down-regulated DEGs DAD1 and STUB1 in high-grade NMI cancer and invasive bladder cancer. Our study indicates that NONHSAG013805 and NONHSAG009271 may play key roles in bladder cancer via co-expressing with EIF3E and MYL12A , respectively. Moreover, NONHSAG034203 may be involved in low-grade NMI bladder cancer via targeting ADM5 , while NONHSAG045391 may contribute to high-grade NMI and invasive bladder cancer via targeting DAD1 and STUB1 . [ABSTRACT FROM AUTHOR]