miR-215-5p Plays a Key Role in Suppressing Vascular Invasion and Recurrence in Hepatocellular Carcinoma by Blocking Vasculogenic Mimicry

Bibliographic Details
Title: miR-215-5p Plays a Key Role in Suppressing Vascular Invasion and Recurrence in Hepatocellular Carcinoma by Blocking Vasculogenic Mimicry
Authors: Heng Zhang, Xi Lan, Liquan Cai, Xunfeng Gao, Feng Gao, Dan Yu, Jinlong Zhang, Jinhui Zhang, Qinwen Tai
Source: Frontiers in Bioscience-Elite, Vol 16, Iss 1, p 6 (2024)
Publisher Information: IMR Press, 2024.
Publication Year: 2024
Collection: LCC:Environmental sciences
LCC:Microbiology
Subject Terms: hepatocellular carcinoma, mir-215-5p, zeb2, vasculogenic mimicry, vascular invasion, recurrent metastasis, Environmental sciences, GE1-350, Microbiology, QR1-502
More Details: Background: This research explores the significance of miR-215-5p and vasculogenic mimicry (VM) in forecasting the prognosis for hepatocellular carcinoma (HCC). Methods: We analyzed HCC-associated miRNA expression profiles using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Samples included tissue and blood from 80 early-stage HCC patients and serum from 120 healthy individuals. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure miR-215-5p and zinc finger E-box binding homeobox 2 (ZEB2) gene expressions. Hematoxylin and eosin (H&E) and CD34/Periodic Acid-Schiff (PAS) double staining assessed VM presence in HCC tissue sections. Bioinformatics tools predicted interactions between miR-215-5p and ZEB2, confirmed through luciferase reporter assays. We also examined the impact of miR-215-5p or ZEB2 overexpression on HCC cell invasion, migration, and VM formation using scratch, Transwell invasion assays, and Matrigel 3D cultures. Results: Bioinformatics analysis indicated that miR-215-5p was under-expressed in HCC, particularly in cases with vascular invasion, which correlated with worse patient outcomes. In contrast, ZEB2, targeted by miR-215-5p, was overexpressed in HCC. RT-qPCR validated these expression patterns in HCC tissues. Among the HCC patients, 38 were VM positive and 42 VM negative. Logistic regression highlighted a negative correlation between miR-215-5p levels and VM positivity in HCC tissues and a positive correlation for ZEB2 with VM positivity and tumor vascular invasion. Lower miR-215-5p levels were linked to increased HCC recurrence and metastasis. Both bioinformatics analysis and luciferase assays demonstrated a direct interaction between miR-215-5p and ZEB2. Enhancing miR-215-5p levels reduced ZEB2 expression, consequently diminishing invasion, migration, and VM formation of the HCC cells in vitro. Conclusions: miR-215-5p expression inversely correlates with VM occurrence in HCC tissues, while ZEB2 expression shows a direct correlation. By targeting ZEB2, miR-215-5p may hinder VM in HCC tissues, helping to prevent vascular invasion and HCC recurrence. Thus, miR-215-5p emerges as a vital prognostic indicator for predicting vascular invasion and recurrence in HCC.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1945-0494
Relation: https://www.imrpress.com/journal/FBE/16/1/10.31083/j.fbe1601006; https://doaj.org/toc/1945-0494
DOI: 10.31083/j.fbe1601006
Access URL: https://doaj.org/article/35b7c3f1017045f9ae5bcc4b7355e17b
Accession Number: edsdoj.35b7c3f1017045f9ae5bcc4b7355e17b
Database: Directory of Open Access Journals
More Details
ISSN:19450494
DOI:10.31083/j.fbe1601006
Published in:Frontiers in Bioscience-Elite
Language:English