Clinical significance and effect of MTDH/AEG-1 in bladder urothelial cancer: a study based on immunohistochemistry, RNA-seq, and in vitro verification.

Background: Overexpression of metadherin/astrocyte elevated gene-1 (MTDH/AEG-1) has been implicated in various cancers. However, the clinical significance and the potential biological functions of MTDH/AEG-1 in bladder urothelial carcinoma (BUC) are not established.

Methods: In this study, the expression of MTDH/AEG-1in BUC was measured using the Cancer Genome Atlas (TCGA) database and immunohistochemistry, together with a meta-analysis, to investigate the expression and diagnostic value of MTDH/AEG-1. The possible association between MTDH/AEG-1 expression and the viability, proliferation, and apoptosis in BUC cell lines (T24, HT1376, and RT4) was also assessed in vitro by viability, MTS, colony formation, and caspase-3/7 assays, as well as Hoechst 33342 and propidium iodide (PI) double staining.

Results: MTDH/AEG-1 expression was significantly higher in BUC tissues than in normal bladder tissues, according to the TCGA and immunohistochemistry results, and these findings were verified by the meta-analysis. Functional knockdown of MTDH/AEG-1 suppressed BUC cell growth and induced apoptosis. Bioinformatics analyses indicated an involvement of MTDH/AEG-1 in several processes, including RNA binding, protein transport, intracellular transport, and the insulin signaling pathway.

Conclusion: We hypothesize that MTDH/AEG-1 could play essential roles in BUC, especially in cell growth and apoptosis, via the insulin signaling pathway."