Kaiying Yang1, Xuepeng Zhang2, Linwen Chen3, Siyuan Chen4, Yi Ji5. 1. Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, #37 Guo-Xue-Xiang, Chengdu, 610041, China. 2. Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China. 3. College of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China. 4. Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China. siy_chen@163.com. 5. Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, #37 Guo-Xue-Xiang, Chengdu, 610041, China. jijiyuanyuan@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. 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. CONCLUSIONS: 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.
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