MiR-193 inhibits bladder cancer progression by targeting N-myc
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ABSTRACT:
PROVIDER: PRJNA691550 | ENA |
REPOSITORIES: ENA
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Project description:Growing evidence has indicated that miR-193 is involved in the initiation and progression of malignancy, such as bladder cancer, hepatocellular carcinoma, renal cell carcinoma, and colorectal cancer. Nevertheless, the mechanisms of miR-193 in the development of metastatic bladder cancer remains unknown. In the current study, we clarified the association of miR-193/N-myc was implicated in cancer metastasis. miR-193 expression increased in metastatic bladder cancer biopsies compared to the primary cases. Moreover, the elevation of miR-193 was correlated with the invasiveness, lymph node metastasis, and advanced stages of bladder cancer significantly. Downregulation of miR-193 by shRNA hampered proliferation and migration while inducing cell apoptosis. Furthermore, miR-193 sponged N-myc and diminished miR-103 expression. Overexpression of miR-193 released oncogene N-myc expression, leading to the promotion of cell proliferation and migration. Besides, knockout of miR-193 suppressed tumor growth in the human T24 mice models. Briefly, the present findings suggested that miR-193-N-myc were novel promising pathways for conquering bladder cancer progression.
2021-01-13 | GSE164682 | GEO
Project description:Tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein (TRAIP), a RING domain-containing E3 ligase, has emerged as a key player in safeguarding genome integrity and is closely linked to cancer. Here, we discovered that TRAIP exhibits low expression in bladder cancer (BLCA), which correlates with poor prognosis. TRAIP exerts inhibitory effects on bladder cancer cell proliferation and migration both in vitro and in vivo. MYC serves as a newly identified target for TRAIP, with direct interaction leading to the promotion of K48 polyubiquitination at K428/430 lysine residues, subsequently resulting in proteasome-dependent degradation and downregulation of MYC's transcriptional activity. This process effectively hinders the progression of bladder cancer. Restoration of MYC expression rescues the suppressed proliferation and migration of bladder cancer cells induced by TRAIP. Furthermore, our investigation also demonstrates that MYC binds to the transcriptional start region of TRAIP, exerting regulatory control over TRAIP transcription. Consequently, this interaction establishes a negative feedback loop that prevents excessive expression of MYC. In summary, our study uncovers a novel mechanism by which TRAIP inhibits the progression of bladder cancer through the ubiquitinated degradation of MYC.
2023-12-28 | GSE237002 | GEO
Project description:Hitherto, most studies on POLD1 have mainly focused on the effect of POLD1 inactivation mutation in tumors. Nonetheless, the mechanism underlying high POLD1 expression in tumorigenesis remains elusive. Herein, we substantiated the pro-carcinogenic role of POLD1 in bladder cancer (BLCA) and found that POLD1 expression is related to malignancy and prognosis of BLCA. Next, we demonstrated that POLD1 could promote proliferation and metastasis of BLCA via MYC. Mechanistically, we demonstrated that POLD1 was able to stabilize MYC in a manner independent of DNA polymerase activity. POLD1 attenuated the FBXW7-mediated ubiquitination degradation of MYC by directly binding to the MYC homology box 1 domain competitively with FBXW7. Moreover, we found that POLD1 can form a complex with MYC to promote the transcriptional activity of MYC. MYC could also transcriptionally activate POLD1, forming a POLD1-MYC positive feedback loop to enhance the pro-carcinogenic effect of POLD1-MYC on BLCA. Overall, our study suggests a novel MYC-driven mechanism for BLCA, and POLD1 has the potential as a biomarker for BLCA.
2023-03-29 | PXD040806 | Pride
Project description:Purpose: To investigate the tumor-promoting role of STIL in bladder cancer. Method: We established the STIL knockout cell line in which the target gene was knocked out by sgRNA. RNA was extracted from cells using trizol reagent(Invitrogen) Result: Through RNA-sequencing analysis of wild-type and STIL-deficient UMUC3 cell lines, the downstream signaling pathways that STIL may be involved in were determined. We found that the PI3K/AKT/mTOR signaling pathway and c-myc were significantly inactivated when STIL was knocked out in bladder cancer. Our RNA-sequencing analysis results showed that the downstream molecules of c-myc (MCM4, HSPD1, EIF2S2, DDX21, DDX18, CBX3, ABCE1) were significantly down-regulated in bladder cancer cells after knockout. Conclusion: STIL enhances the PI3K/AKT/mTOR pathway, which consequently upgraded the expression of c-myc, ultimately promoting the occurrence and progression of bladder cancer C. STIL may suggest potential utility for bladder cancer therapy.
2023-08-01 | GSE211756 | GEO
Project description:Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Although the application of immune checkpoint, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), achieved definite efficacy, the effect of immunotherapy for bladder cancer is still not very satisfactory. Therefore, it is very urgent to develop new targets to expand the options of immunotherapies. In this study, we utilized single cell sequencing to explore the cell composition and detected a subset of Treg cells with high expression of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and interleukin (IL)-32 molecules. Certainly, anti-tumor immune response was suppressed by this subset of Treg cells and IL-32 promoted the bladder cancer metastasis. Nevertheless, targeting TIGIT not only could reverse immunosuppression through restoring anti-tumor immune response mediated by T cells but suppressed the secretion of IL-32 and inhibited the metastasis of bladder cancer cells. Thus, our study provided a novel insight into the immunosuppression in bladder cancer and developed the TIGIT as the novel target for immunotherapy of bladder cancer. Furthermore, we also illustrated mechanism of the dual effect of targeting TIGIT in bladder cancer and revealed the metastasis-promoting effect of IL-32 in bladder cancer. Taken together, the discovery raises the possibility of TIGIT targets against bladder cancer from the bench to the bedside.
2022-01-31 | GSE186520 | GEO
Project description:Ten-Eleven Translocation 1 (TET1) is a member of methylcytosine dioxygenase, which catalyse 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) that promote the demethylation process. The diminished expression of TET1 protein and 5-hmC in many tumors indicate a critical role for the maintenance of cell stability. However, role of TET1 in bladder cancer development remains unclear. Here we found that TET1 expression was downregulated in bladder cancer tissues compared with normal urothelium and was inversely related to patient overall survival. TET1 silencing in bladder cancer cells increase proliferation and inhibited cell migration and invasion while its re-expression inhibits their proliferation and the growth of tumor xenografts. Furthermore, we found that TET1 binds to the promoter of the TSG to maintain its hypomethylated which interacts with β-catenin and suppress its nuclear translocation, thus inhibiting β-catenin transcriptional activity and downstream genes. In conclusion, TET1 acts as a tumor suppressor gene in bladder cancer cells by suppressing β-catenin signaling. This study may facilitate efforts to therapeutic strategy for patients with bladder cancer.
2020-06-16 | GSE137646 | GEO
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Project description:Methods: Mouse bladder tumor organoids with Trp53, Pten, Rb1 mutation and Myc, KrasG12D amplification were treated with 10μM SRT1720 and Vehicle for 12 hours respectively. RNA libraries of SRT1720 and vehicle treated mouse bladder organoids were constructed according to standard Illumina protocols, and bulk RNA-seq were performed using Illumina NovaSeq 6000 sequencing platform.
2021-09-01 | GSE155525 | GEO
Project description:Sinorhizobium fredii USDA 193 genome sequencing
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