KUMSAL AYSE TEKIRDAG Biological Sciences and Bioengineering, PhD Dissertation, 2015 Thesis Jury Assoc.Prof.Devrim GOZUACIK (Thesis Advisor), Prof. Huveyda BASAGA, Assoc. Prof. Ali KOSAR, Prof. Engin ULUKAYA, Assoc. Prof. Elif Damla ARISAN Date & Time: 23th, July 2015 – 11.00 Place: FENS L062 Keywords : microRNA, autophagy, regulation, cancer Abstract Autophagy is a cellular survival pathway that can be activated via different stresses and dysregulation of autophagy might result in pathological states. Therefore, discovery of novel pathways regulating autophagy is crucial. miRNAs as non-protein-coding RNAs control cellular levels of genes and recently, role of microRNAs in regulation of autophagy is under investigation. Regulation of stress-induced autophagy through several novel microRNAs via targeting crucial autophagy genes were shown in this thesis. Analysis of these miRNAs in terms their of i) effect on autophagic activity, ii) target prediction and iii) target validation through various in vitro tests in different cancer cell lines were carried out. Besides, the role of autophagy-regulating microRNAs in cancer formation and tumorigenesis has been under investigation to enlighten the role of these microRNAs in early stages of cancer formation in vivo. Altogether, the outcomes of this thesis are: 1) Introduction of novel autophagy regulating miRNAs to the field 2) Underlining the importance of these miRNAs in the control of autophagic responses of cells and role in tumorigenesis. Therefore, discovery of miRNA-mediated regulation of autophagy which provides a dynamic mechanism under various stress conditions adds another layer of regulation for critical cell death and survival decisions in health and disease.