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Onko (Subject) / 8. Culig (Lesson)

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• Which markers are up- or down-regulated during epithelial to mesenchymal transition (EMT)? Repressor of E-cadherin: transcription factors Snail 1 and Snail 2 TGF-beta: induce Snail 1 and Snail 2 microRNAs emerge as potent regulators of EMT and MET
• Which transcription factors regulate EMT? TGF-beta Snail, slug – zinc-finger transcription factors
• How do oncogenic miRNA (with examples) regulate EMT? MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers.
• How can tumor suppressive miRNA (with examples) regulate EMT? miR-29b is suppressed in prostate cancer (reexpression of miR-29b inhibits metastasis of prostate cancer cells in a mouse model miR-29b modulates the EMT markers in prostate cancer cells loss of tumor suppressive miRNA during EMT in prostate cancer) . miR-29b -> modulates EMT markers -> downregulates N-Cadherin, Twist, Snail -> all of which promote EMT → suppresses EMT and its reexpression is associated with reinstallation of cellular adhesion
• Describe experimental therapy approaches to target EMT SD-208 reverses TGF-𝛃- induced EMT. SD-208 decreases Brachyury expression and enhances chemotherapy sensitivity of human carcinoma cells.

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