RESUMEN
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with increasing incidence in western countries. Most HCC patients have advanced cancer at the time of diagnosis due to the asymptomatic nature of early-stage HCC and do not qualify for potentially curative surgical treatment, thus, highlighting the need for new therapeutic strategies. Long noncoding RNAs (lncRNAs) comprise a large and heterogeneous group of non-protein coding transcripts that play important regulatory roles in numerous biological processes in cancer. In this study, we performed RNA sequencing of liver biopsies from ten HCC, ten hepatitis C virus-associated HCC, and four normal livers to identify dysregulated lncRNAs in HCC. We show that the lncRNA p53-upregulated-regulator-of-p53-levels (PURPL) is upregulated in HCC biopsies and that its expression is p53-dependent in liver cancer cell lines. In addition, antisense oligonucleotide-mediated knockdown of PURPL inhibited cell proliferation, induced apoptosis, and sensitized HepG2 human HCC cells to treatment with the chemotherapeutic agent doxorubicin. In summary, our findings suggest that PURPL could serve as a new therapeutic target for reversing doxorubicin resistance in HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/genética , Proliferación Celular/genética , Doxorrubicina/farmacología , Línea Celular , Regulación Neoplásica de la Expresión Génica , Línea Celular TumoralRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Although significant progress has been made in recent years to treat DLBCL patients, 30%-40% of the patients eventually relapse or are refractory to first line treatment, calling for better therapeutic strategies for DLBCL. Long non-coding RNAs (lncRNAs) have emerged as a highly diverse group of non-protein coding transcripts with intriguing molecular functions in human disease, including cancer. Here, we review the current understanding of lncRNAs in the pathogenesis and progression of DLBCL to provide an overview of the field. As the current knowledge of lncRNAs in DLBCL is still in its infancy, we provide molecular signatures of lncRNAs in DLBCL cell lines to assist further lncRNA research in DLBCL.