Abstract
Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of hepatocellular carcinoma (HCC) remains largely unknown. We performed a comprehensive microarray analysis of lncRNA expression in human HCC samples. After validation in 108 HCC specimens, we identified a differentially expressed novel tumor suppressive lncRNA termed amine oxidase, copper containing 4, pseudogene (AOC4P). The level of AOC4P expression was significantly downregulated in 68% of HCC samples and negatively correlated with advanced clinical stage, capsule invasion and vessel invasion. Low AOC4P expression correlated with poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that AOC4P overexpression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). RNA immunoprecipitation assays demonstrated that AOC4P binds to vimentin and promotes its degradation. Animal model experiments confirmed the ability of AOC4P to suppress tumor growth and metastasis. Taken together, our findings suggest that AOC4P lncRNA acts as an HCC tumor suppressor by enhancing vimentin degradation and suppressing the EMT. By clarifying the mechanisms underlying HCC progression, these findings promote the development of novel therapeutic strategies for HCC.
Highlights
hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide
To identify long non-coding RNAs (lncRNAs) that are involved in the progression of HCC, total RNA was isolated from HCC samples obtained from 3 patients and matched normal adjacent tissues and was subjected to microarray analysis (Affymetrix GeneChip® Human Gene 2.0)
We selected 10 lncRNAs displaying a fold-change in expression of >4 and analyzed their expression via real-time polymerase chain reaction (PCR) in 15 paired HCC and adjacent noncancerous tissues
Summary
HCC is the fifth most common cancer and the third most common cause of cancer-related death worldwide. Approximately 8,000 new cases of HCC are diagnosed in Taiwan every year. Approximately 2% of transcripts can be translated into proteins, whereas 98% of transcripts are noncoding RNAs (ncRNAs). Short ncRNAs are less than 200 nucleotides in length and include small interfering RNA (siRNA, 21–25 bp), piwi-associated RNA (piRNA, 23–30 bp), and microRNA (miRNA, 21–25 bp) [5, 6]. Recent studies have indicated that ncRNAs regulate various physiologic functions, including development, proliferation, migration, and apoptosis [5, 7]. 30% of human genes are regulated by miRNA, and miRNA deregulation is associated with several types of cancer [7,8,9,10,11]. The biological function and clinical significance of lncRNAs in cancer remain largely unexplored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
