Infantile 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. The 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. In 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. The 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.

中文翻译：

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mRNA和长非编码RNA的芯片表达谱以及PFK-1在婴儿血管瘤中的潜在作用

小儿血管瘤（IH）是儿童中最常见的良性肿瘤。长的非编码RNA（lncRNA）在肿瘤发生中起关键作用。但是，尚未对IH中lncRNA的表达水平和生物学功能进行深入研究。这项研究旨在分析lncRNA和mRNA在增殖和渐进性IH中的表达特征。通过微阵列分析鉴定了lncRNA和mRNA在增殖和渐进的IH中的表达谱。随后，进行了详细的生物信息学分析。最后，进行了实时定量聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）分析，以验证微阵列结果。总共鉴定出146个差异表达（DE）lncRNA和374个DE mRNA。通过生物信息学分析，DE mRNAs主要富集于血管生成相关的生物学过程（BPs）和途径中。另外，鉴定了与代谢有关的BP（例如“糖原生物合成过程”和“代谢过程”）和途径（例如“氧化磷酸化”）。由42个DE lncRNA和217个DE mRNA构建了一个lncRNA-mRNA共表达网络。预测十二个lncRNA具有顺式调节的靶基因。通过使用5个随机选择的lncRNA和13个mRNA的qRT-PCR验证了微阵列分析结果。IHC结果表明，在增生性IH中，LOXL2和FPK-1均比在渐进性IH中表现出更高的蛋白表达水平。此外，抑制PFK-1可以抑制血管瘤衍生的内皮细胞增殖和迁移，诱导细胞停滞，并减少葡萄糖摄取以及乳酸和ATP的产生。这些发现表明，鉴定出的DE lncRNA和mRNA可能与IH的发病机制有关。本文提供的数据可以改善我们对IH发展的理解，并为进一步研究IH的潜在机制提供指导。