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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumor types and the third leading cause of cancer-related mortality worldwide [1,2]
Several differentially expressed lincRNAs were identified in the two hepatocellular carcinoma (HCC) samples compared to adjacent normal tissues in our microarray analysis
LINC01488 displaying low expression in HCC samples was confirmed via Quantitative Reverse Transcription-PCR (qRT-PCR) (Figure 1A)
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumor types and the third leading cause of cancer-related mortality worldwide [1,2]. Cells 2020, 9, 1504 effective therapeutic strategies [3,4]. The majority of HCC patients present symptoms at advanced stages when metastasis has occurred. Metastasis interferes with the treatment options and presents a significant cause of liver failure and tumor recurrence. Clarification of the mechanisms involved in HCC progression is essential to facilitate the development of effective novel therapeutic targets. LincRNAs are frequently dysregulated in various cancers and are shown to have multiple functions in several biological processes such as modulation of proliferation and metastasis and cellular development and differentiation [2,6,7]. Recent studies have revealed opposing roles of lincRNAs as either proto-oncogenes (TUG1, HOTAIR) or tumor suppressor genes (LINC01488, MEG3) in tumorigenesis [8,9,10]
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.
