Vimentin epigenetic deregulation in Bladder Cancer associates with acquisition of invasive and metastatic phenotype through epithelial-to-mesenchymal transition

Abstract

Bladder cancer (BlCa) is the ninth most common cancer worldwide, associated with significant morbidity and mortality. Thus, understand the biological mechanisms underlying tumour progression is of great clinical significance. Vimentin (VIM) is (over)expressed in several carcinomas, putatively in association with EMT. We have previously found that VIM promoter methylation accurately identified BlCa and VIM expression associated with unfavourable prognosis. Herein, we sought to investigate VIM expression regulation and its role in malignant transformation of BlCa. Analysis of tissue samples disclosed higher VIM transcript, protein, and methylation levels in BlCa compared with normal urothelium. VIM protein and transcript levels significantly increased from non-muscle invasive (NMIBC) to muscle-invasive (MIBC) cases and to BlCa metastases. Inverse correlation between epithelial CDH1 and VIM, and a positive correlation between mesenchymal CDH2 and VIM were also observed. In BlCa cell lines, exposure to demethylating agent increased VIM protein, with concomitant decrease in VIM methylation. Moreover, exposure to histone deacetylases pan-inhibitor increased the deposit of active post-translational marks (PTMs) across VIM promoter. In primary normal urothelium cells, lower levels of active PTMs with concomitant higher levels of repressive marks deposit were observed. Finally, VIM knockdown in UMUC3 cell line increased epithelial-like features and decreased migration and invasion in vitro, decreasing tumour size and angiogenesis in vivo. We demonstrated that VIM promoter is epigenetically regulated in normal and neoplastic urothelium, which determine a VIM switch associated with EMT and acquisition of invasive and metastatic properties. These findings might allow for development of new, epigenetic-based, therapeutic strategies for BlCa.

Sulforaphane Inhibits Adhesion and Migration of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro

“…Vimentin expression requires consideration since we found up-regulation when T24 cells were treated with SFN. This contrasts with reports indicating a correlation between vimentin expression and acquiring an invasive and metastatic bladder cancer phenotype [ 28 ]. Other investigators have demonstrated that spatial vimentin organization is critical for mediating cell migration [ 29 ].…”

LINC01559 promotes lung adenocarcinoma metastasis by disrupting the ubiquitination of VIM

“…Huang' research underscores the oncogenic role of VIM in hepatocellular carcinoma cells (42). Furthermore, research by Sara Monteiro-Reis et al highlights the expression of VIM associates with invasive and metastatic phenotype of bladder cancer (43). Our research discovered that knocking down VIM expression signi cantly curbed the migration and invasion ability of LUAD cell lines, which indicating that VIM was a functional protein to promote the metastasis of LUAD.…”

Landscape of Exhausted T Cells in Tuberculosis Revealed by Single-Cell Sequencing

“…For example, H1FX has mainly been highlighted to be associated with cancer to date ( 35 , 36 ), whereas ZFP36L2 was reported to induce apoptosis and inhibit cell proliferation ( 37 , 38 ). VIM is involved in cell attachment, migration, and signal transduction ( 39 ). Here, we separated the exhausted subsets of CD4 + and CD8 + T cells into distinct subclusters via further unsupervised analysis.…”