RGD Reference Report - A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression. - Rat Genome Database

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A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression.

Authors: Chen, Haiyang  Hu, Liang  Luo, Zaili  Zhang, Jian  Zhang, Cunzhen  Qiu, Bijun  Dong, Liwei  Tan, Yexiong  Ding, Jin  Tang, Shanhua  Shen, Feng  Li, Zhong  Wang, Hongyang 
Citation: Chen H, etal., Mol Cancer. 2015 Nov 4;14:186. doi: 10.1186/s12943-015-0454-6.
RGD ID: 151347618
Pubmed: PMID:26538215   (View Abstract at PubMed)
PMCID: PMC4634191   (View Article at PubMed Central)
DOI: DOI:10.1186/s12943-015-0454-6   (Journal Full-text)


BACKGROUND: Aberrant expression of A20 has been reported in several human malignancies including hepatocellular carcinoma (HCC). However, its clinical relevance and potential role in HCC remain unknown.
METHODS: Quantitative PCR, Western blots and immunohistochemistry analyses were used to quantify A20 expression in HCC samples and cell lines. The correlation of A20 expression with clinicopathologic features was analyzed in a cohort containing 143 patients with primary HCC. Kaplan-Meier curves were used to evaluate the association between A20 expression and patient survival. Functional studies were performed to determine the effects of A20 on proliferation and metastasis of HCC cells in vitro and in vivo.
RESULTS: Expression of A20 was increased in HCC tissues and cell lines. Increased expression of A20 was negatively correlated with the tumor size, TNM stage, tumor thrombus formation, capsular invasion and serum AFP levels. Patients with higher A20 expression had a prolonged disease-free survival and overall survival than those with lower A20 expression. Forced expression of A20 significantly inhibited the proliferative and invasive properties of HCC cells both in vitro and in vivo, whereas knockdown of A20 expression showed the opposite effects. Further studies revealed that expression of A20 was inversely correlated with Twist1 levels and NF-κB activity in HCC tissues and cell lines. A20-induced suppression of proliferation and migration of HCC cells were mainly mediated through inhibition of Twist1 expression that was regulated at least partly by A20-induced attenuation of NF-κB activity.
CONCLUSIONS: Our results demonstrate that A20 plays a negative role in the development and progression of HCC probably through inhibiting Twist1 expression. A20 may serve as a novel prognostic biomarker and potential therapeutic target for HCC patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma amelioratesIEP 151347618mRNA and protein:increased expression:liver (human)RGD 
hepatocellular carcinoma amelioratesISOTNFAIP3 (Homo sapiens)151347618; 151347618mRNA and protein:increased expression:liver (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnfaip3  (TNF alpha induced protein 3)

Genes (Mus musculus)
Tnfaip3  (tumor necrosis factor, alpha-induced protein 3)

Genes (Homo sapiens)
TNFAIP3  (TNF alpha induced protein 3)


Additional Information