Long non-coding RNA AOC4P suppresses hepatocellular carcinoma metastasis by enhancing vimentin degradation and inhibiting epithelial-mesenchymal transition

Tumor progression
DOI: 10.18632/oncotarget.4344 Publication Date: 2015-09-16T17:47:25Z
ABSTRACT
// Tong-Hong Wang 1 , Yong-Shiang Lin 2 Ying Chen Chau-Ting Yeh 3 Yen-lin Huang Tsung-Han Hsieh Tzong-Ming Shieh 4 Chuen Hsueh 1, Tse-Ching Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Department of Anatomic Pathology, University School Medicine, Hepato-Gastroenterology, Liver Research Center, Dental Hygiene, College Health Care, China Medical University, Taichung, Correspondence to: Chuen-Hsueh, e-mail: ch9211@adm.cgmh.org.tw Chen, ctc323@adm.cgmh.org.tw Keywords: long non-coding RNA (lncRNA), hepatocellular carcinoma (HCC), epithelial-mesenchymal transition (EMT), metastasis Received: April 09, 2015      Accepted: June 12, Published: 23, 2015 ABSTRACT Increasing evidence indicates that RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function lncRNAs in progression (HCC) remains largely unknown. We performed a comprehensive microarray analysis lncRNA expression human HCC samples. After validation 108 specimens, we identified differentially expressed novel tumor suppressive termed amine oxidase, copper containing 4, pseudogene (AOC4P). The level AOC4P was significantly downregulated 68% samples negatively correlated with advanced clinical stage, capsule invasion vessel invasion. Low poor prognostic outcomes, serving as an independent factor for HCC. In vitro functional assays indicated overexpression reduced proliferation, migration by inhibiting (EMT). immunoprecipitation demonstrated binds to vimentin promotes its degradation. Animal model experiments confirmed ability suppress growth metastasis. Taken together, our findings suggest acts suppressor enhancing degradation suppressing EMT. By clarifying mechanisms underlying progression, these promote development therapeutic strategies
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