Long Non-Coding RNA ZEB2-AS1 Promotes Hepatocellular Carcinoma Progression by Regulating The miR-582-5p/ FOXC1 Axis

Objectives: Long non- coding RNAs (lncRNAs) feature prominently in tumors. Reportedly, lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) is aberrantly expressed in a variety of tumors. The present study was aimed to explore ZEB2- AS1 functions and determine mechanism in hepatocellular carcinoma (HCC) progression. Materials and Methods: In this experimental study, expressions of ZEB2-AS1, microRNA ( miR)-582- 5p and forkhead box C1 (FOXC1) mRNA in HCC tissues and cell lines were detected via quantitative reveres transcription polymerase chain reaction ( qRT-PCR). After establishing gain- and loss-of-functions models, cell counting kit-8, 5-bromo-2'-deoxyuridine (BrdU), Transwell assays and flow cytometry analysis were conducted to examine HCC cell multiplication, migration, invasion and apoptosis, respectively. The targeted relationship between miR-5825p and ZEB2-AS1 was verified via dual-luciferase reporter gene assay. Western blot was utilized for detecting FOXC1 expression in HCC cells after selectively regulating ZEB2-AS1 and miR-582-5p. Results: In HCC tissues and cells, ZEB2-AS1 expression was increased. High ZEB2- AS1 expression was related to relatively large tumor volume, increased tumor-node-metastasis (TNM) stage and positive lymph node metastasis of the patients. ZEB2- AS1 overexpression facilitated HCC cell multiplication, migration, invasion and suppressed apoptosis, while ZEB2-AS1 knock-down caused the opposite effects. It was also confirmed that ZEB2- AS1 could competitively bind with miR- 582- 5p to repress its expression, and indirectly up-regulate FOXC1 expression level in HCC cells. Conclusion: The current study revealed that ZEB2-AS1 was over-expressed in HCC tissues and cells. It also upregulated FOXC1, through sponging miR-582-5p, to promote HCC progression. This provides new perspectives for elucidating the pathogenesis of HCC.