A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E
Authors: Chau-Ting Yeh
Tzu-Kang Lin
Hsiang-Cheng Chi
Syuan-Ling Lin
Wei-Jan Chen
Yang-Hsiang Lin
Kwang-Huei Lin
Journal: Cells (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: cyclin E; hepatocellular carcinoma; long intergenic non-coding RNAs; microRNA-124-3p/138-5p; tumor suppressor
Affiliations: Translational Medicine Research Center, China Medical University Hospital, Taichung 404, Taiwan., Department of Biochemistry, School of Medicine, Chang-Gung University, Taoyuan 333, Taiwan., Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan 333, Taiwan., Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan., Neurosurgery, Fu Jen Catholic University Hospital and School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan., Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan., Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.

Abstract:  Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that has the potential to inhibit progression of human hepatocellular carcinoma (HCC). Our experiments disclosed long intergenic non-protein coding RNA 1488 (LINC01488) as a key negative regulator of HCC. Clinically, patients with high LINC01488 expression displayed greater survival rates and better prognosis. In vitro and in vivo functional assays showed that LINC01488 overexpression leads to significant suppression of cell proliferation and metastasis in HCC. Furthermore, LINC01488 bound to cyclin E to induce its ubiquitination and reduced expression of vimentin mediated by both miR-124-3p/miR-138-5p. Our results collectively indicate that LINC01488 acts as a tumor suppressor that inhibits metastasis and tumorigenesis in HCC via the miR-124-3p/miR-138-5p/vimentin axis. Furthermore, LINC01488 interacts with and degrades cyclin E, which contributes to its anti-tumorigenic activity. In view of these findings, we propose that enhancement of LINC01488 expression could be effective as a potential therapeutic strategy for HCC. 

Retracted: No

PubPeer comments:
 Images of different treatments in Fig 7 and S3 seem identical. ![file] The figures don t seem to meet the minimal resolution requirement by Cells . How are the policies enforced by Cells? , 
 The authors would like to correct the unintentional mistakes during preparation the figures for publication. The authors have provided three independent data to the journal. The conclusions are the same without change. The quality of images has met the requirement of the  Cells . Further, the editorial office (Cells) has accepted our request to correct them. The updated version has been shown online. The link is following: https: www.mdpi.com 2073-4409 9 6 1504 ,