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Figure 4 | Journal of Biomedical Science

Figure 4

From: MicroRNA: a prognostic biomarker and a possible druggable target for circumventing multidrug resistance in cancer chemotherapy

Figure 4

miR-34a mediates paclitaxel resistance via both direct and indirect mechanisms . (a) Schematic representation of direct and indirect mechanisms underlying miR-34a-mediated paclitaxel resistance. Direct pathway: miR-34a inhibit proliferation of paclitaxel-resistant PC3PR cells by directly suppressing the cell cycle regulators cyclin D1 and CDK6. Indirect pathway: miR-34a can enhance apoptosis by indirectly reducing expression of the anti-apoptotic gens (SIRT1 & BCL2) via modulating HuR [41]. (b) Indirect mechanism of miR-200c/-205-mediated EMT and resistance to apoptosis. Key signals that lead to EMT trigger expression of a variety of transcriptional repressors, including ZEB1, ZEB2/SIP1, Snail, and Twist. These repressors are the intracellular mediators of EMT by binding to E-box elements of genes, such as CDH1, that encode for the adhesion protein E-cadherin. After binding, they recruit histone deacetylases and other corepressors to facilitate transcriptional repression of E-cadherin. Reduced cellular E-cadherin expression subsequently will lead to loss of cell-cell adhesion and a series of other events, eventually leading to an invasive mesenchymal and drug resistance phenotype [43].

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