Microarray expression profile of mRNAs and long noncoding RNAs and the potential role of PFK-1 in infantile hemangioma

Kaiying Yang,Siyuan Chen,Xuepeng Zhang,Yi Ji,Linwen Chen

doi:10.1186/s13008-020-00069-y

Abstract

BackgroundInfantile hemangioma (IH) is the most common benign tumor in children. Long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis. However, the expression levels and biological functions of lncRNAs in IH have not been well-studied. This study aimed to analyze the expression profile of lncRNAs and mRNAs in proliferating and involuting IHs.MethodsThe expression profiles of lncRNAs and mRNAs in proliferating and involuting IHs were identified by microarray analysis. Subsequently, detailed bioinformatics analyses were performed. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analyses were conducted to validate the microarray results.ResultsIn total, 146 differentially expressed (DE) lncRNAs and 374 DE mRNAs were identified. The DE mRNAs were enriched mostly in angiogenesis-related biological processes (BPs) and pathways by bioinformatics analysis. In addition, metabolism-related BPs (e.g., “glycogen biosynthetic process” and “metabolic process”) and pathways (e.g., “oxidative phosphorylation”) were identified. A lncRNA-mRNA co-expression network was constructed from 42 DE lncRNAs and 217 DE mRNAs. Twelve lncRNAs were predicted to have cis-regulated target genes. The microarray analysis results were validated by qRT-PCR using 5 randomly selected lncRNAs and 13 mRNAs. The IHC results revealed that both LOXL2 and FPK-1 exhibited higher protein expression levels in proliferating IH than in involuting IH. Moreover, inhibition of PFK-1 could suppress hemangioma-derived endothelial cell proliferation and migration, induce cell arrest, and reduce glucose uptake and lactate and ATP production.ConclusionsThe findings suggest that the identified DE lncRNAs and mRNAs may be associated with the pathogenesis of IH. The data presented herein can improve our understanding of IH development and provide direction for further studies investigating the mechanism underlying IH.

Highlights

Infantile hemangioma (IH) is the most common benign tumor in children, with a prevalence of 4–5% [1]
Long noncoding RNAs (LncRNAs) and mRNA expression profiles in IH To explore the expression level profiles of Long noncoding RNAs (lncRNAs) and mRNAs in IH, lncRNA and mRNA microarray analyses were performed with six proliferating IH samples and four involuting IH samples (Fig. 1)
A volcano plot was generated to provide an overview of the differentially expressed (DE) lncRNAs and mRNAs in our microarray data (Fig. 2a, b)

Summary

Introduction

Infantile hemangioma (IH) is the most common benign tumor in children, with a prevalence of 4–5% [1]. IH is usually absent at birth and exhibits a characteristic growth pattern with a proliferating phase lasting for 1 year after birth, with the most rapid growth at 5–8 weeks, followed by spontaneous involution lasting up to 5 years [3]. Yang et al Cell Div (2021) 16:1 proliferating phase, the IH will enlarge, become more elevated and develop a rubbery consistency; in contrast, in the involuting phase, the IH will flatten and shrink from the center outward [4]. Infantile hemangioma (IH) is the most common benign tumor in children. The expression levels and biological functions of lncRNAs in IH have not been well-studied.

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