Abstract
Anillin (ANLN) is an actin-binding protein essential for assembly of cleavage furrow during cytokinesis. Although reportedly overexpressed in various human cancers, its role in hepatocellular carcinoma (HCC) is unclear. To address this issue, we confirmed that in 436 liver samples obtained from surgically removed HCC tissues, higher ANLN expression was detected in tumor tissues than in adjacent non-tumor tissues of HCC as measured by immunohistochemistry, quantitative real-time PCR and western blotting. Correlation and Kaplan-Meier analysis revealed that patients with higher ANLN expression were associated with worse clinical outcomes and a shorter survival time, respectively. Moreover, ANLN inhibition resulted in growth restraint, reduced colony formation, and a lower sphere number in suspension culture. Mechanistically, ANLN deficiency induced an increasing number of multinucleated cells along with the activation of apoptosis signaling and DNA damage checkpoints. Furthermore, HBV infection increased ANLN expression by inhibiting the expression of microRNA (miR)-15a and miR-16-1, both of which were identified as ANLN upstream repressors by targeting its 3’ untranslated region. Thus, we conclude that ANLN promotes tumor growth by ways of decreased apoptosis and DNA damage. Expression level of ANLN significantly influences the survival probability of HCC patients and may represent a promising prognostic biomarker.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for approximately 700,000 deaths per year [1]
These results indicated that ANLN overexpression is a common feature in human HCC
We demonstrated that ANLN was upregulated in HCC tissues and cell lines
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for approximately 700,000 deaths per year [1]. Current treatment options for HCC are limited and generally ineffective. Curative treatments including liver transplantation and hepatic resection are only eligible for 20% of HCC patients due to late stage diagnosis. Frequent relapse occurs in HCC patients even after receiving radical surgery. The 5-year overall survival rate of HCC patients, in intermediate stage and advanced stages, remains www.aging‐us.com extremely low [2]. Better understanding of the molecular mechanism related to liver carcinogenesis and further studies of HCC oncogenes would help to develop new diagnostic and therapeutic strategies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
