New LncRNAs in Chronic Hepatitis C progression: from fibrosis to hepatocellular carcinoma

Autor(es)

Ferrasi, Adriana Camargo ^{[1, 2]} ; Fernandez, Geysson Javier ^[3] ; Tommasini Grotto, Rejane Maria ^{[2, 4]} ; Silva, Giovanni Faria ^[1] ; Goncalves, Joao ^[5] ; Costa, Marina C. ^[6] ; Enguita, Francisco J. ^[6] ; de Moura Campos Pardini, Maria Ines ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Med, Dept Internal Med, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Ctr Blood Transfus, HC FMB, Mol Biol Lab, Botucatu, SP - Brazil

^[3] Univ Antioquia, UdeA, Fac Med, Grp Inmunovirol, Medellin - Colombia

^[4] Sao Paulo State Univ UNESP, Coll Agr Sci, Dept Bioproc & Biotechnol, Botucatu, SP - Brazil

^[5] Univ Lisbon, Fac Farm, iMed Res Inst Med, Lisbon - Portugal

^[6] Univ Lisbon, Fac Med, Inst Med Mol Joao Lobo Antunes, P-1649028 Lisbon - Portugal

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 JUN 18 2020.
• Citações Web of Science: 0

Resumo

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world, and about 80% of the cases are associated with hepatitis B or C. Genetic and epigenetic alterations are accumulated over decades of chronic injury and may affect the functioning of tumor suppressor genes and protooncogenes. Studies have evidenced the role of Long non-coding RNAs (LncRNA) with oncogenic or tumor suppressor activities, suggesting a great potential in the treatment, diagnosis or indicator of prognosis in cancer. In this context, the aim of this study was to evaluate the global expression profile lncRNA in hepatic tissue samples with different stages of fibrosis associated with chronic hepatitis C, HCC and normal liver, in order to identify new lncRNAs that could contribute to study the progression of hepatic fibrosis to HCC associated with chronic hepatitis C. RNA-Seq was performed on Illumina NextSeq platform to identify lncRNAs expressed differently in 15 patients with chronic hepatitis C, three patients with HCC and three normal liver specimens. When the pathological tissues (fibrosis and carcinoma) were compared to normal hepatic tissue, were identified 2, 6 e 34 differentially expressed lncRNAs in moderate fibrosis, advanced fibrosis and HCC, respectively. The carcinoma group had the highest proportion of differentially expressed lncRNA (34) and of these, 29 were exclusive in this type of tissue. A heat map of the deregulated lncRNA revealed different expression patterns along the progression of fibrosis to HCC. The results showed the deregulation of some lncRNA already classified as tumor suppressors in HCC and other cancers, as well as some unpublished lncRNA whose function is unknown. Some of these lncRNAs are dysregulated since the early stages of liver injury in patients with hepatitis C, others overexpressed only in tumor tissue, indicating themselves as candidates of markers of fibrosis progression or tumor, with potential clinical applications in prognosis as well as a therapeutic target. Although there are already studies on lncRNA in hepatocellular carcinoma, this is the first study conducted in samples exclusively of HCV-related liver and HCV HCC. (AU)

• Processo FAPESP: 13/21214-9 - Avaliação de polimorfismos genéticos na progressão da infecção de pacientes monoinfectados e coinfectados com os vírus da imunodeficiência humana (HIV) e vírus da hepatite C (VHC)
• Beneficiário: Rejane Maria Tommasini Grotto
• Modalidade de apoio: Auxílio à Pesquisa - Regular