The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma

Chang, Lei; Li, Cuicui; Guo, Tao; Wang, Haitao; Ma, Weijie; Yuan, Yufeng; Liu, Quanyan; Ye, Qifa; Liu, Zhisu

doi:10.1186/s13046-016-0286-2

Cited by 65 publications

(64 citation statements)

References 27 publications

(30 reference statements)

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“…The mRNA surveillance pathway detects and degrades abnormal mRNAs which is essential for tumourigenesis and immune response 44. For instance, RNA surveillance factor UPF1 has been reported regulating HCC pathogenesis by targeting Smad7 45. In line with our findings, previous studies have shown that the mRNA surveillance pathway is required for oxidative stress tolerance, cancer, virus infection and immune response 46.…”

Section: Discussionsupporting

confidence: 87%

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

et al. 2018

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BackgroundT cell dysfunction occurs in many diseases, especially in chronic virus infection and cancers. However, up to now, little is known on the distinctions in T cell exhaustion between cancer and chronic virus infection. The objective of this study is to explore the transcriptional similarities and differences in exhausted CD8 +T cell between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).MethodsRNA sequencing was performed to compare the transcriptome of CD8 +T cells isolated from healthy donors’ blood, tumour tissues of patients with HCC and chronic HBV infected HCC patients’ paracancerous tissues. DESeq2 algorithm was used to determine differentially expressed genes. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted for in-depth analysis of these differentially expressed genes.ResultsA total number of 2109 and 2203 genes were differentially expressed in patients with chronic HBV infection and HCC, respectively. Comparing these two groups of differentially deregulated genes, we found that nearly half of them were shared, and these shared genes were further classified into several functional categories, such as metabolic process, binding and intracellular organelle. KEGG analysis revealed that these shared deregulated genes were involved in many important pathways such as Parkinson’s disease, oxidative phosphorylation and messenger RNA surveillance. Interestingly, we reported that chronic HBV infection specific deregulated genes were mainly enriched in graft versus host disease, allograft rejection, phenylalanine, tyrosine and tryptophan biosynthesis pathways. Whereas, HCC-specific deregulated genes were highly enriched in oxidative phosphorylation, thyroid cancer and endometrial cancer pathways.ConclusionOur study demonstrated that T cell dysfunction associated with HCC and chronic HBV infection shares high similarities, however, each possesses its own features in terms of specific genes and signalling pathways. Uncovering the differences of T cells dysfunction would facilitate our understanding the diseases pathogenesis and developing innovative therapies in the future.

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Section: Discussionsupporting

confidence: 87%

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

et al. 2018

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“…Previous study has verified that hypermethylatìon of tumor suppressor genes contributes to gastric tumorigenesis [20] and UPF1 hypermethylation has been shown in hepatocellular carcinoma [21]. To investigate the underlying mechanism responsible for UPF1 downregulation in gastric tumor, we detected whether hypermethylation was involved in the progression.…”

Section: Resultsmentioning

confidence: 99%

“…More importantly, UPF1 also modulates RNA transcripts in a NMD-independent way. For example, UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma [21]. And UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance [35].…”

Section: Discussionmentioning

confidence: 99%

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

Li¹,

Geng²,

Ren³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. Methods: Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion. Additionally, sodium bisulfate sequencing was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1. Results: The expression of UPF1 was significantly downregulated in gastric cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 increased nonsense-mediated mRNA decay (NMD) efficiency and thus led to downregulation of MALAT1. Conclusion: Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer.

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“…Pancreatic squamous carcinoma cells have mutations in the Upf1 gene, allowing the synthesis of mutated dominant negative p53, functionally correlating NMD inhibition with cancer [145]. Loss of function or overexpression of NMD proteins is also associated with several other cancer types, including colorectal cancer, hepatocellular carcinoma and neuroblastoma [146][147][148]. NMD is also involved in the adaptation to stress response [149,150].…”

Section: Htlv-1-associated Pathologies How Can Nmd Inhibition Impactmentioning

confidence: 99%

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

Prochasson¹,

Jalinot²,

Mocquet³

2020

Preprint

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Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition.HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct longterm impact remains to be investigated.

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The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma

Cited by 65 publications

References 27 publications

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

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