- Background/Aims: Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related deaths worldwide, not least due to its high chemoresistance. The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), localised in nuclear paraspeckles, has been shown to enhance chemoresistance in several cancer types. Since data on NEAT1 in HCC chemosensitivity are completely lacking and chemoresistance is linked to poor prognosis, we aimed to study NEAT1 expression in HCC chemoresistance and its link to HCC prognosis.
Methods: NEAT1 expression was determined in either sensitive, or sorafenib, or doxorubicin resistant HepG2, PLC/PRF/5, and Huh7 cells by qPCR. Paraspeckles were detected by immunostaining of paraspeckle component 1 (PSPC1) in cell culture and in a cohort of HCC patients. PSPC1 expression was correlated with clinical data. The expression of transcript variants of NEAT1 and transcripts encoding the paraspeckle-associated proteins was analysed in the TCGA liver cancer data set.
Results: NEAT1 was overexpressed in all three sorafenib and doxorubicin resistant cell lines. Paraspeckles were present in all chemoresistant cells, whereas no signal was detected in the sensitive cells. Expression of NEAT1 transcripts as well as transcripts encoding PSPC1, NONO, and RBM14 was increased in tumour tissue. Expression of PSPC1, NONO, and RBM14 transcripts was significantly associated with poor survival, whereas NEAT1 expression was not. Immunohistochemical analysis revealed that nuclear and cytoplasmic PSPC1-positivity was significantly associated with shorter overall survival of HCC patients.
Conclusion: Our data show an induction of NEAT1 in HCC chemoresistance and a high correlation of transcripts encoding paraspeckle-associated proteins with poor survival in HCC. Therefore, NEAT1, PSPC1, NONO, and RBM14 might be promising targets for novel HCC therapies, and the paraspeckle-associated proteins might be clinical markers and predictors for poor survival in HCC.
MetadatenAuthor: | Sonja KeßlerORCiDGND, Kevan Hosseini, Usama Khamis Hussein, Kyoung Min Kim, Markus ListORCiDGND, Christina S. Schultheiß, Marcel Holger SchulzORCiDGND, Stephan Laggai, Kyu Yun Jang, Alexandra Kathrin KiemerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-503188 |
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URL: | https://www.cellphysiolbiochem.com/Articles/000055/ |
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DOI: | https://doi.org/10.33594/000000055 |
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ISSN: | 1421-9778 |
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ISSN: | 1015-8987 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30946555 |
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Parent Title (English): | Cellular physiology and biochemistry |
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Publisher: | Cell Physiol Biochem Press GmbH & Co KG |
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Place of publication: | Düsseldorf |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2019 |
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Date of first Publication: | 2019/04/05 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2019/05/23 |
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Tag: | Actinomycin D; Chemosensitivity; Chemotherapy; Liver cancer; MALAT1; NEAT2; Therapy response; lncRNA; mRNA decay; mRNA stability |
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Volume: | 52 |
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Issue: | 4 |
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Page Number: | 15 |
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First Page: | 787 |
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Last Page: | 801 |
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Note: | This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. |
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HeBIS-PPN: | 450825000 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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