In:
Molecular Oncology, Wiley, Vol. 11, No. 9 ( 2017-09), p. 1225-1240
Abstract:
Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma ( HCC ). Absent in melanoma 2 ( AIM 2) has been implicated in inflammation and carcinogenesis, although its role in HCC metastasis remains unknown. In the present study, we show that AIM 2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM 2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds. In vitro studies demonstrated that AIM 2 expression was modulated by hepatitis B virus X protein ( HB x) at transcriptional and post‐translational levels. HB x overexpression markedly blocked the expression of AIM 2 at mRNA and protein levels by enhancing the stability of Enhancer of zeste homolog 2 ( EZH 2). Furthermore, HB x interacted with AIM 2, resulting in an increase of AIM 2 degradation via ubiquitination induction. Functionally, knockdown of AIM 2 enhanced cell migration, formation of cell pseudopodium, wound healing and tumor metastasis, whereas reintroduction of AIM 2 attenuated these functions. The loss of AIM 2 induced the activation of epithelial‐mesenchymal transition ( EMT ). Fibronectin 1 ( FN 1) was found to be a downstream effector of AIM 2, with its expression reversely modulated by AIM 2. Silencing of FN 1 significantly halted cell migration induced by AIM 2 depletion. These data demonstrate that HB x‐induced loss of AIM 2 is associated with poor outcomes and facilitates HCC metastasis by triggering the EMT process. The results of the present study therefore suggest that AIM 2 is a potential prognostic biomarker in hepatitis B virus‐related HCC , as well as a possible therapeutic target for tumor metastasis.
Type of Medium:
Online Resource
ISSN:
1574-7891
,
1878-0261
DOI:
10.1002/mol2.2017.11.issue-9
DOI:
10.1002/1878-0261.12090
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2322586-5
