TY  - JOUR
A1  - Keßler, Sonja
A1  - Hosseini, Kevan
A1  - Hussein, Usama Khamis
A1  - Kim, Kyoung Min
A1  - List, Markus
A1  - Schultheiß, Christina S.
A1  - Schulz, Marcel Holger
A1  - Laggai, Stephan
A1  - Jang, Kyu Yun
A1  - Kiemer, Alexandra Kathrin
T1  - Hepatocellular carcinoma and nuclear paraspeckles : induction in chemoresistance and prediction for poor survival
T2  - Cellular physiology and biochemistry
N2  - 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.
KW  - Liver cancer
KW  - Chemosensitivity
KW  - Chemotherapy
KW  - Therapy response
KW  - lncRNA
KW  - MALAT1
KW  - NEAT2
KW  - mRNA stability
KW  - mRNA decay
KW  - Actinomycin D
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50318
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-503188
UR  - https://www.cellphysiolbiochem.com/Articles/000055/
SN  - 1421-9778
SN  - 1015-8987
N1  - 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.
VL  - 52
IS  - 4
SP  - 787
EP  - 801
PB  - Cell Physiol Biochem Press GmbH & Co KG
CY  - Düsseldorf
ER  -