Role of microRNAs in human pharmacogenomics / Omaima Salah Eldin Somida Awad Ali ; Supervised Samy A. Abdelazim , Kamal Maamoun Eldeib , Hebatallah A. Darwish

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

The purpose of this research study is to assess the regulatory and protective role of miR-26a on lipid metabolism and progression of non alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) in human HepG2 and VL-17a cells loaded with free fatty acids (FFA) alone or with ethanol (EtOH), respectively. Lentivirus expresses miR-26a or miR control (CN) was used to transduce the cells to establish stable cell lines. Gain or loss of function using miR-26a inhibitor (IN) was used to compare triglyceride content (TG), levels of total cholesterol (CL), total antioxidant capacity (TAC), malondialdehyde (MDA) as well as level of apoptosis. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to assess the mRNA levels of lipogenesis, TG synthesis, storage genes, PKC-e, inflammatory and fibrogenic markers, autophagy besides endoplasmic reticulum (ER) stress markers after gaining or losing the function of miR-26a. The upregulation of miR-26a downregulated TG, CL and MDA levels, through its regulating action on genes involved in de novo lipogenesis (DNL), TG synthesis, storage, PKC-e, ER stress, inflammatory and fibrogenic markers. Nevertheless, there was a marked increment in mRNA expression of autophagic marker genes

Issued also as CD