USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells

Liao, Yuning; Shao, Zhenlong; Liu, Yuan; Xia, Xiaohong; Deng, Yuanfei; Yu, Cuifu; Sun, Wenshuang; Kong, Weiyao; He, Xiaoyue; Liu, Fang; Chen, Guoxing; Tang, Daolin; Gan, Hui-Li; Liu, Jinbao; Huang, Hongbiao

doi:10.1186/s13046-021-02008-3

Cited by 36 publications

(23 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have shown that in the antiviral response signaling pathway of type I interferon, the deubiquitinase USP1 interacts with TBK1 to deubiquitinate TBK1, enhance the expression of downstream type I interferon, and inhibits viral replication ( Yu et al., 2017 ). A previous study found an interaction between RPS16 and USP1 in hepatoma cells ( Liao et al., 2021b ). Also, our result showed that knockdown of RPS16 in the cell obviously increased the phosphorylation of TBK1 ( Figure 7G ).…”

Section: Resultsmentioning

confidence: 85%

MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response

Wang

Xia

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Given the frequent emergence of drug-resistant influenza virus strains and new highly pathogenic influenza virus strains, there is an urgent need to identify new antiviral drugs and targets. We found that influenza A virus (IAV) infection caused a significant decrease of microRNA let-7 expression in host cells; that overexpression of let-7 increased interferon expression and effectively inhibit IAV infection; and that let-7 targets the 3’-untranslated region (UTR) of the ribosomal protein 16 (RPS16) gene, decreasing its expression. Knocking down the expression of RPS16 increased the expression of type I interferon and inhibited viral replication. The present study uncovered the regulatory effect of let-7b and let-7f on influenza A infection, which is a potential biomarker of IAV infection. In addition, let-7 may be a promising therapeutic agent against influenza A.

show abstract

Section: Resultsmentioning

confidence: 85%

MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response

Wang

Xia

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Recently, increasing DUBs were identified as tumor promoters via deubiquitinating and stabilizing certain oncoproteins in cancers, and were proposed as novel therapeutic targets. In this study, we showed that ARV-771 can downregulate multiple DUBs in HCC, including USP1, USP8, USP10, USP13, and USP18, which have been implicated in the tumorigenesis and progression by regulating certain substrates ( Cai et al, 2017 ; Gao et al, 2020 ; Zhu et al, 2020 ; Liao et al, 2021b ; Zhu et al, 2021 ). Therefore, we hypothesized that the reduction of USP1, USP8, USP10, USP13, and USP18 may all involve in the ARV-771-induced growth inhibition in HCC.…”

Section: Disccussionmentioning

confidence: 80%

“…Recently, the roles of DUBs have been highlighted in the progression of HCC. For example, the ubiquitin-specific peptidase 1 (USP1) may promote proliferation and migration of HCC via controlling the protein stability of ribosomal protein S16 (RPS16) ( Liao et al, 2021b ). Additionally, the USP14 can also facilitate cell proliferation and migration by maintaining HIF1-α stability in HCC ( Lv et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

ARV-771 Acts as an Inducer of Cell Cycle Arrest and Apoptosis to Suppress Hepatocellular Carcinoma Progression

Deng

Chen

et al. 2022

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer with limited treatment options and extremely poor prognosis worldwide. Recently, the proteolysis targeting chimeras (PROTACs), which aim to induce proteasome-mediated degradation of interesting proteins via recruiting E3 ligases, have become the advanced tools and attractive molecules for cancer treatment. However, the anticancer effects of PROTACs in HCC remain to be clarified. Here, we evaluate the anticancer activity of ARV-771, a previously reported PROTAC compound designed for bromodomain and extra-terminal domain (BET) proteins, in HCC. We show that ARV-771 suppresses the cell viability and colony formation of HCC cells via arresting cell cycle progression and triggering apoptosis. Further investigations reveal that ARV-771 notably downregulates multiple non-proteasomal deubiquitinases which are critical to the development of cancers. Additionally, HCC cells can decrease their sensitivity to ARV-771 via activating the MEK/ERK and p38 MAPKs. ARV-771 also inhibits HCC progression in vivo. Moreover, we show that ARV-771 and sorafenib, a Raf inhibitor that clinically used for targeted therapy of liver cancer, can synergistically inhibit the growth of HCC cells. Overall, this study not only explores the anticancer activity of ARV-771 and its underlying mechanisms in HCC, but also deepens our understanding of deubiquitinases, MAPKs, cell cycle, and apoptosis induction in cancer therapy.

show abstract

“…Importantly, the high expression of USP1 and RPS16 in liver tissue is a prognostic factor for poor survival of HCC patients. 31 …”

Section: Discussionmentioning

confidence: 99%

Analysis of Gene Co-Expression Network to Identify the Role of CD8 + T Cell Infiltration-Related Biomarkers in High-Grade Glioma

Feng¹,

Li²,

Tian³

et al. 2022

IJGM

View full text Add to dashboard Cite

Background High-grade glioma is a type of heterogeneous lethal brain tumor most common in adults. At present, immune checkpoint inhibitors (ICIs) are being considered for first-line therapeutics for malignant GBM. Nonetheless, molecular markers for malignant GBM are unavailable at present. As a result, it is important to explore molecular markers related to immunity for GBM. Materials and Methods The present study adopted a deconvolution algorithm for quantifying immunocyte composition and measuring gene expression, and used weighted gene co-expression network analysis (WGCNA) to analyze GBM expression data obtained from Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) databases. Thereafter, key CD8+ T cell infiltration-related genes and modules were identified, and database analysis was conducted to verify the therapeutic and immune features of the selected genes. Results From this study, CD8+ T cell-related modules were identified. By using consistent clustering analysis, two panels of genes (red and green) with the highest correlation with CD8+ T cells infiltration were used to construct high-, low-expression groups, silent and/or mixed group of T cell infiltrations. In the high and low CD8+ T cell infiltration groups, a total of 535 differential genes were obtained, of which ten genes (RPS5, RPS6, FAU, RPS19, RPS23, RPS15A, RPS29, RPS14, RPS16, RPS27A) were identified through protein–protein interactions and co-expression network analysis. Post Cox regression and Kaplan–Meier (K-M) survival analysis, RPS5, RPS6, and RPS16 were selected as candidate prognostic biomarkers related to CD8+ T cells. Conclusion The three associated genes RPS5, RPS6, and RPS16 were markedly related to degree of T cell infiltration and immune-related activated. We identified their potential biomarkers and therapeutic targets associated with the extent of CD8+ T cell infiltration in GBM.

show abstract

USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells

Cited by 36 publications

References 46 publications

MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response

MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response

ARV-771 Acts as an Inducer of Cell Cycle Arrest and Apoptosis to Suppress Hepatocellular Carcinoma Progression

Analysis of Gene Co-Expression Network to Identify the Role of CD8 + T Cell Infiltration-Related Biomarkers in High-Grade Glioma

Contact Info

Product

Resources

About