“FUNCTIONAL IMPACT OF EPIGENETIC REGULATION IN HEPATOCARCINOMA: DEVELOPMENT OF COMBINED NANOVECTORIZATION OF miRNAS/lnCRNAS AND DRUGS USEFUL IN EXPERIMENTAL LIVER CANCER MODEL” (PI19/01266)
Hepatocarcinoma (HCC) is the six most frequent neoplasia, the third cause of death by cancer, and the 7% of registered malignancies. Nowadays, 50-60% of patients are diagnosed at intermediate (BCLC and advanced (BCLC C) stages of the disease. The candidate will determine lncRNA profile in cell lysate and extracellular vesicles (EVs) released by liver cancer cells in different stages of cell differentiation, and under drug pressure by doxorubicin and tyrosine kinase receptor inhibitors (Sorafenib, Regorafenib, Lenvatinib o Cabozantinib), that will be functionally validated by the overexpression of mimetics or anti-miRNAs/lncRNAs in the capacity to regulate cell death and proliferation, translational profile, mRNA expression, mitochondrial function, migration and invasiveness in 2D and 3D culture. The project will also prospectively identify lncRNAs profiles in exosomes and circulating tumor cells (CTCs) from blood obtained from patients at the intermediate and advanced stages.
The therapeutic potential of the selected epigenetic profile will be evaluated in one experimental model of hepatocarcinogenesis based on the targeted nanovectorization to asialoglycoprotein receptors (ASGPR) using β-cyclodextrin (β-CD), and with the overexpression of selected lncRNAs combined with drugs in a single vector. The antitumoral activity will be assessed in an experimental model of hepatocarcinogenesis based on the orthotopic implant of HCC cells at poorly differentiated stage.
El grupo se compromete a financiar al candidato mediante fondos del grupo hasta consecución beca FPU/PFIS 2021.
Expediente académico superior a 2,5.
CANDIDATOS INTERESADOS DIRIGIRSE A:
Dr. Jordi Muntané Relat
Laboratorio 209 (Instituto de Biomedicina de Sevilla, IBiS)
Telf: 955923122, 607730985
e-mail: jmuntane-ibis en us.es
PLAZO ENVÍO PROPUESTAS:
15 Octubre 2020