IMR Press / FBE / Volume 16 / Issue 1 / DOI: 10.31083/j.fbe1601006
Open Access Original Research
miR-215-5p Plays a Key Role in Suppressing Vascular Invasion and Recurrence in Hepatocellular Carcinoma by Blocking Vasculogenic Mimicry
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1 General Surgery Center, Shenzhen Hospital, Southern Medical University, 518000 Shenzhen, Guangdong, China
2 Clinical Laboratory Center, Shenzhen Hospital, Southern Medical University, 518000 Shenzhen, Guangdong, China
*Correspondence: (Jinhui Zhang); (Qinwen Tai)
These authors contributed equally.
Front. Biosci. (Elite Ed) 2024, 16(1), 6;
Submitted: 12 August 2023 | Revised: 12 November 2023 | Accepted: 27 December 2023 | Published: 27 February 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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.

hepatocellular carcinoma
vasculogenic mimicry
vascular invasion
recurrent metastasis
20210505225917001/Shenzhen Baoan District Science and Technology Plan Basic Research Project
Fig. 1.
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