scholarly journals Overexpression of the RD RNA binding protein in hepatitis C virus-related hepatocellular carcinoma

2012 ◽  
Vol 28 (2) ◽  
pp. 728-734 ◽  
Author(s):  
MICHIHISA IIDA ◽  
NORIO IIZUKA ◽  
RYOUICHI TSUNEDOMI ◽  
MASAHIRO TSUTSUI ◽  
SHIN YOSHIDA ◽  
...  
2018 ◽  
Vol 9 (11) ◽  
pp. 930-944 ◽  
Author(s):  
Huang Cao ◽  
Kaitao Zhao ◽  
Yongxuan Yao ◽  
Jing Guo ◽  
Xiaoxiao Gao ◽  
...  

2004 ◽  
Vol 24 (18) ◽  
pp. 7878-7890 ◽  
Author(s):  
Jong Heon Kim ◽  
Ki Young Paek ◽  
Sang Hoon Ha ◽  
Sungchan Cho ◽  
Kobong Choi ◽  
...  

ABSTRACT Translational initiation of hepatitis C virus (HCV) mRNA occurs by internal entry of ribosomes into an internal ribosomal entry site (IRES) at the 5′ nontranslated region. A region encoding the N-terminal part of the HCV polyprotein has been shown to augment the translation of HCV mRNA. Here we show that a cellular protein, NS1-associated protein 1 (NSAP1), augments HCV mRNA translation through a specific interaction with an adenosine-rich protein-coding region within the HCV mRNA. The overexpression of NSAP1 specifically enhanced HCV IRES-dependent translation, and knockdown of NSAP1 by use of a small interfering RNA specifically inhibited the translation of HCV mRNA. An HCV replicon RNA capable of mimicking the HCV proliferation process in host cells was further used to confirm that NSAP1 enhances the translation of HCV mRNA. These results suggest the existence of a novel mechanism of translational enhancement that acts through the interaction of an RNA-binding protein with a protein coding sequence.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3397
Author(s):  
Leyre Silva ◽  
Josune Egea ◽  
Lorea Villanueva ◽  
Marta Ruiz ◽  
Diana Llopiz ◽  
...  

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered.


EBioMedicine ◽  
2019 ◽  
Vol 45 ◽  
pp. 155-167 ◽  
Author(s):  
Wei Dong ◽  
Zhi-hui Dai ◽  
Fu-chen Liu ◽  
Xing-gang Guo ◽  
Chun-mei Ge ◽  
...  

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