Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin
| Autor: | Tsinat Berhane, Anja Holm, Kasper Thystrup Karstensen, Andreas Petri, Mirolyuba Simeonova Ilieva, Henrik Krarup, Mogens Vyberg, Marianne Bengtson Løvendorf, Sakari Kauppinen |
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| Rok vydání: | 2021 |
| Předmět: |
Multidisciplinary
Carcinoma Hepatocellular Liver Neoplasms Doxorubicin/pharmacology Apoptosis Carcinoma Hepatocellular/drug therapy Liver Neoplasms/drug therapy Cell Line Gene Expression Regulation Neoplastic Cell Proliferation/genetics SDG 3 - Good Health and Well-being Doxorubicin Apoptosis/genetics Cell Line Tumor Humans Tumor Suppressor Protein p53/genetics RNA Long Noncoding Tumor Suppressor Protein p53 RNA Long Noncoding/metabolism Cell Proliferation |
| Zdroj: | Berhane, T, Holm, A, Karstensen, K T, Petri, A, Ilieva, M S, Krarup, H, Vyberg, M, Løvendorf, M B & Kauppinen, S 2022, ' Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin ', Scientific Reports, vol. 12, no. 1, 19502 . https://doi.org/10.1038/s41598-022-23802-9 Berhane, T, Holm, A, Karstensen, K T, Petri, A, Ilieva, M S, Krarup, H, Vyberg, M, Løvendorf, M B & Kauppinen, S 2022, ' Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin ', Scientific Reports, vol. 12, 19502 . https://doi.org/10.1038/s41598-022-23802-9 |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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