Effect of miR-451a on metabolomic profiles of hepatocellular carcinoma cell lines

• Grant number: 19/17003-9
• Support type: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): October 21, 2019
• Effective date (End): January 20, 2020
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Patricia Pintor dos Reis
• Grantee: Carolina Fazio Campos
• Supervisor abroad: Luis Alejandro Jose Mur
• Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Research place: Aberystwyth University, Wales
• Associated to the scholarship: 18/06354-2 - Functional validation of microRNA target genes in hepatocellular carcinoma, BP.MS

Abstract

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer death and the sixth most frequent type of cancer worldwide. The main risk factor of HCC is hepatic cirrhosis and the predisposing factors consist of metabolic diseases and chronic infections of hepatitis B (HBV) and C (HCV) virus. MicroRNAs are small noncoding RNAs that regulate gene transcription or translation by interacting with the 3'-untranslated region of a target gene. Several miRNAs have been associated with HCC development, and changes in miRNA expression alter important biological processes necessary for cancer development and progression. Among these miRNAs, miR-451a has been related with inhibition of cell growth and proliferation, increased apoptosis and decreased cell migration of HCC cell lines. However, the mechanisms by which miR-451 affects tumorigenesis has yet to be elucidated. Metabolomics analysis has been reported as a valuable tool to assist the identification of biomarkers for early detection of cancer, including HCC. Therefore, the aim of this study is to evaluate the effect of increased of miR-451a in HCC cell lines positive for HBV (Hep 3B and PCL/PRF/5) and negative (HEP G2) on the HCC metabolome using Flow Infusion Electrospray Ionization High Resolution Mass Spectrometry (FIE-HRMS). We will assess if the metabolite changes detected in tumor cell are related to the miR-451a target genes (FMNL3, SPC25, BUB1B, KIF2A, KLC2, and PLEKHG2). Thus, the cell lines will be transfected with miR-451a mimics or negative control and the metabolites will be extracted for FIE-HRMS. The data will be assessed by MetaboAnalyst 4.0 and analyzed by Human Metabolomics Database and KEGG. This analysis will help to verify if miR-451a can be used as a potential new biomarker in HCC and indicate how its mis-regulation affects the HCC metabolome. (AU)