Molecular characterization of low grade and high grade bladder cancer
Authors: Apollo, Alessandro; Ortenzi, Valerio; Scatena, Cristian; Zavaglia, Katia; Aretini, Paolo; Lessi, Francesca; Franceschi, Sara; Tomei, Sara; Sepich, Carlo Alberto; Viacava, Paolo; Mazzanti, Chiara Maria; Naccarato, Antonio Giuseppe
Background Bladder cancer (BC) is the 9th most common cancer diagnosis worldwide. Low grade (LG) represents 70% of all BCs, characterized by recurrence and rare ability (10-15%) to progress to high grade (HG) and invade. The remaining 30% is high grade (HG), fast invasive BC, which is resistant to therapy. Identifying biomarkers for predicting those tumors able to progress is a key goal for patient outcome improvement. This study focuses on the most promising prognostic markers. Materials and methods TP53 and FGFR3 mutational status, Survivin, CK19, CK20, E-cadherin and CD44 gene expression analysis were performed on 66 BCs. Results Survivin was found associated to tumor grade (p<0.05). Moreover, Survivin correlated with CD44 in TP53 wild type (p = 0.0242) and FGFR3 wild type (p = 0.0036) tumors. In particular the Survivin-CD44 correlation was associated to HG FGFR3 wild type BCs (p = 0.0045). Unsupervised hierarchical clustering based on gene expression data identified four distinct molecular groups reflecting the patient histology (p = 0.038). Conclusion We suggest Survivin, both as a biomarker associated to G3 BCs but negatively related to TP53 mutational status, and as a potential novel therapeutic target.
Identification of microRNA transcriptome reveals that miR-100 is involved in the renewal of porcine intestinal epithelial cells
SCIENCE CHINA-LIFE SCIENCES
Authors: Zou, Lijun; Xiong, Xia; Yang, Huansheng; Wang, Kexing; Zhou, Jian; Lv, Dinghong; Yin, Yulong
MicroRNAs play important roles in various cellular processes, including differentiation, proliferation and survival. Using a pig model, this study sought to identify the miRNAs responsible for crypt-villus axis renewal of the small intestinal epithelium. Compared to the villus upper cells, there were 15 up-regulated and 41 down-regulated miRNAs in the crypt cells of the jejunum. Notably, we found that miR-100 was expressed more in the villus upper cells than in the crypt cells, suggesting an effect on intestinal epithelium differentiation. Overexpression of miR-100 increased the activity of alkaline phosphatase, confirming that miR-100 promoted IPEC-J2 cell differentiation. MiR-100 can inhibit cell proliferation as evidenced by CCK-8 and cell cycle assay results. We also showed that miR-100 significantly inhibited the migration of IPEC-J2 cells and promoted cell apoptosis through caspase-3-dependent cleavage of Bcl-2. Furthermore, FGFR3 was identified as a potential target of miR-100 by bioinformatics analysis. We confirmed that overexpression of miR-100 suppressed FGFR3 expression in IPEC-J2 cells by directly targeting the FGFR3 3-UTR. This is the first report of miRNAs acting on the renewal of the intestinal crypt-villus axis. Our results also showed that miR-100 promotes the differentiation and apoptosis, and inhibits the proliferation and migration of enterocytes of pigs.