Research Papers:
Long non-coding RNA AOC4P suppresses hepatocellular carcinoma metastasis by enhancing vimentin degradation and inhibiting epithelial-mesenchymal transition
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Abstract
Tong-Hong Wang1, Yong-Shiang Lin2, Ying Chen1, Chau-Ting Yeh3, Yen-lin Huang2, Tsung-Han Hsieh1, Tzong-Ming Shieh4, Chuen Hsueh1,2, Tse-Ching Chen1,2
1Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
2Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan
3Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
4Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan
Correspondence to:
Chuen-Hsueh, e-mail: [email protected]
Tse-Ching Chen, e-mail: [email protected]
Keywords: long non-coding RNA (lncRNA), hepatocellular carcinoma (HCC), epithelial-mesenchymal transition (EMT), metastasis
Received: April 09, 2015 Accepted: June 12, 2015 Published: June 23, 2015
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.
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