The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression

• DOI: 10.1038/cddis.2014.367
• Publication Date: 2014-09-04T14:20:50Z
• Authors: L Lv; H Deng; Y Li; C Zhang; X Liu; Q Liu; D Zhang; L Wang; Y Pu; H Zhang; Y He; Y Wang; Y Yu; T Yu; J Zhu
• Keywords: Male; 0301 basic medicine; 2. Zero hunger; Mice, Inbred BALB C; Base Sequence; Cell Survival; Molecular Sequence Data; Kruppel-Like Transcription Factors; NF-kappa B; Mice, Nude; Nuclear Proteins; DNA Methylation; Antineoplastic Agents, Phytogenic; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; MicroRNAs; 03 medical and health sciences; Drug Resistance, Neoplasm; Cell Line, Tumor; Animals; Humans; Original Article; 3' Untranslated Regions; DNA Damage

Chemoresistance hinders the curative cancer chemotherapy. To define role of DNA methylation-regulated microRNA (miR) genes in chemoresistance bladder cancer, we performed both methylomic and miRomic analyses a multi-chemosensitive (5637) versus multi-chemoresistant (H-bc) cell line found that miR-193a-3p is hypermethylated/silenced 5637 hypomethylated/expressed H-bc cells. A forced reversal its level turned around cultured cells tumor xenografts nude mice. Three targets: SRSF2, PLAU HIC2, work concert to relay miR-193a-3p's impact on by modulating activities following five signaling pathways: damage, Notch, NF-κB, Myc/Max, Oxidative Stress. In addition mechanistic insights how newly identified miR-193a-3p/SRSF2,PLAU,HIC2/five pathway axis regulates cells, our study provides new set diagnostic targets for guided personalized chemotherapy cancer.