<scp>DNASE1L3</scp> inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

Li, Bo; Ge, Yuzhen; Yan, Weiwei; Gong, Bin; Cao, Kun; Zhao, Rui; Li, Chao; Zhang, Yewei; Jiang, Yi-Heng; Zuo, Shi

doi:10.1111/cpr.13273

Cited by 13 publications

(8 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNase1L3 inhibits proliferation, invasion, and metastasis of HCC. ( 22 ) This study also showed a strong association between DNase1L3 and the clinicopathology of HCC, which is a factor with good prognosis. This study explained the mechanism by which DNase1L3 inhibits tumor progression from the perspective of degrading ecDNA.…”

Section: Discussionsupporting

confidence: 62%

Vitamin D promotes DNase1L3 to degrade ecDNA and inhibit the malignant progression of hepatocellular carcinoma

Zhang,

Qin,

et al. 2023

Preprint

View full text Add to dashboard Cite

Extrachromosomal DNA (ecDNA) is an important carrier of oncogene amplification. However, the degradation mechanism of ecDNA is not well understood. We found that endogenous natural molecular vitamin D (VD) reduces ecDNA and inhibits the progression of hepatocellular carcinoma. VD reduces ecDNA depending on its binding protein GC, which can interact with the endonuclease DNase1L3 and stabilize DNase1L3 protein level. The DNase1L3 protein directly degrades ecDNA, and its N-terminus has a lipophilic region capable of affinity for lipid droplets. Intranuclear lipid droplets are abundantly distributed around ecDNA, so DNase1L3 can affinitize ecDNA through its lipophilic region. VD, as a lipid-soluble molecule, can increase the area of lipid droplets and further improve the degradation of DNase1L3 on ecDNA. Therefore, we designed two mRNA-based therapeutics, DNase1L3 and GC-DNase, both of which had an anti-tumor effect on PDX models. The above results showed that treatments targeting ecDNA in cancer are prospective in clinical practice

show abstract

Section: Discussionsupporting

confidence: 62%

Vitamin D promotes DNase1L3 to degrade ecDNA and inhibit the malignant progression of hepatocellular carcinoma

Zhang,

Qin,

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Cell migration and stem-like properties contribute to the aggressiveness of tumors and poor patient prognosis ( 43 ). Many proteins involved in HCC cell migration are regulated by ubiquitination, such as β-catenin ( 44 ), snail ( 45 , 46 ), and ZEB1 ( 47 ). The EMT marker, Vimentin, may also influence tumor progression.…”

Section: Discussionmentioning

confidence: 99%

UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin

Lu²,

Lei³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor associated with a poor prognosis. Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) has been reported to promote diverse tumors, but little is known about its role in HCC.MethodsExpression levels of UCHL3 in Huh7 and Hep3B cells were measured by qRT-PCR. UCHL3, Vimentin protein levels, and ubiquitination levels were determined by Western blot assay. co-immunoprecipitation, Immunofluorescence, and IHC were used to detect the interaction and expression association between UCHL3 and Vimentin in the cells. Wound healing and Transwell assays were used to measure cell migration. Spheroid formation assay were used to assess stem-like properties.ResultsUCHL3 expression was found to be significantly elevated in HCC and associated with poor prognosis. UCHL3 promoted migration and stem-like properties of HCC cells. Vimentin was identified as a potential de-ubiquitination substrate of UCHL3 and UCHL3 interacted with and promoted the de-ubiquitination of Vimentin, enhancing its stability. Moreover, the suppression of UCHL3 by siRNA or the inhibition by TCID upregulated ubiquitinated Vimentin. Vimentin attenuated the suppression of cell migration caused by knockdown of UCHL3.ConclusionUCHL3 was highly expressed in HCC and functioned as an oncogene. Vimentin is a novel substrate of UCHL3 and its stabilization and de-ubiquitination enhanced HCC cell migration.

show abstract

“…The prognosis of patients with a high DNASE1L3 expression in HCC was better than those with a low expression, as shown by Univariate Cox expression analysis (P<0.001) and Kaplan-Meier survival estimate (P<0.001). DNASE1L3 inhibits HCC by inducing apoptosis and reprogramming glucose metabolism and interacting with β-catenin to promote its ubiquitin degradation pathway ( 26 , 28 ). And DNASE1L3 is a prognostic biomarker associated in cancer ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…DNASE1L3 and DNASE1 can degrade DNA in the serum (19). DNASE1L3 is involved in chromatin degradation in apoptotic or necrotic cells (20)(21)(22)(23)(24)(25)(26)(27)(28). The decrease in DNASE1L3 activity is related to several autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Pan‑cancer analysis of the deoxyribonuclease gene family

Bai

He²,

2023

Mol Clin Oncol

View full text Add to dashboard Cite

Deoxyribonuclease (DNase) is an enzyme that catalyzes the cleavage of phosphodiester bonds in the main chain of DNA to degrade DNA. DNase serves a vital role in several immune-related diseases. The present study linked the expression of DNase with overall survival (OS), performed pan-cancer co-expression analysis, and assessed the association between DNase and immune infiltration subtypes, tumor microenvironment and drug sensitivity through pan-cancer studies. Furthermore, gene expression data and clinical data were downloaded from The Cancer Genome Atlas. Next, through a series of bioinformatics analyses, DNase expression and survival, immune subtypes, tumor microenvironment and drug sensitivity in 33 tumor types were systematically studied. The expression of the DNase gene family was shown to have an apparent intratumoral heterogeneity. The expression of DNase 2, lysosomal (DNASE2) was the highest in tumors, whereas that of DNASE2 β was the lowest. DNase 1-like 3 (DNASE1L3) was mainly downregulated in tumors, whereas the rest of the DNases were mainly upregulated in tumors. The expression of DNase family members was also found to be associated with the OS rate of patients. DNase family genes may serve an essential role in the tumor microenvironment. DNase family gene expression was related to the content of cytotoxic cells, Immunescore, Stromalscore, Estimatescore and Tumorpurity. The present study also revealed that the DNase genes may be involved in the drug resistance of cancer cells. Finally, the correlation between DNase, and clinical stage and tumor microenvironment in hepatocellular carcinoma (HCC) was studied. In addition, the difference in DNASE1L3 expression between HCC and adjacent normal tissues, and the relationship between DNASE1L3 expression and clinical stage was verified by analyzing three groups in a Gene Expression Omnibus dataset and by performing immunohistochemistry. In conclusion, the present study assessed DNase gene expression, analyzed its relationship with patient OS, performed pan-cancer co-expression analysis, and assessed the association between DNase and immune infiltration subtypes, tumor microenvironment and drug sensitivity. The present study also confirmed the value of further laboratory research on DNases and their prospects in clinical cancer treatment.

show abstract

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

Cited by 13 publications

References 53 publications

Vitamin D promotes DNase1L3 to degrade ecDNA and inhibit the malignant progression of hepatocellular carcinoma

Vitamin D promotes DNase1L3 to degrade ecDNA and inhibit the malignant progression of hepatocellular carcinoma

UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin

Pan‑cancer analysis of the deoxyribonuclease gene family

Contact Info

Product

Resources

About