LncRNA-TUG1 promotes the progression of infantile hemangioma by regulating miR-137/IGFBP5 axis

Abstract

Background Previous studies indicated that lncRNA taurine upregulated gene 1 (TUG1) played essential roles in human cancers. This study aimed to investigate its function in infantile hemangioma (IH). Methods A total of 30 pairs of clinical infantile specimens were used in this study. The expression of TUG1 in IH tissues was assessed by quantitative reverse transcriptase PCR (qRT-PCR). Two short hairpin RNA targeting TUG1 (sh-TUG1-1 and sh-TUG1-2) were transfected into hemangioma-derived endothelial cells, HemECs, to block its expression. The effects of TUG1 on HemECs were evaluated by Cell Counting Kit-8 (CCK-8), colony formation assay, wound healing assay, and Transwell assay. The underlying molecular mechanism of TUG1 was investigated by Starbase prediction and luciferase reporter assay and further determined by loss- and gain-of-function approaches. In addition, the role of TUG1 on tumorigenesis of HemECs was confirmed in an in vivo mouse model. Results TUG1 was significantly upregulated in infant hemangioma tissues compared with normal adjacent subcutaneous tissues. The loss- and gain-of-function approaches indicated that TUG1 overexpression promoted proliferation, migration, and invasion of HemECs in vitro, and TUG1 knockdown inhibited the tumorigenesis of HemECs in vivo. Specifically, TUG1 could compete with IGFBP5 for miR137 binding. Rescue experiments further confirmed the role of the TUG1/miR137/IGFBP5 axis in HemECs. Conclusion TUG1 was closely associated with the progression of IH by regulating the miR-137/IGFBP5 axis, which might be a potential target for IH treatment.

GEO Database Screening Combined with In Vitro Experiments to Study the Mechanism of hsa_circ_0003570 in Infantile Hemangiomas

“…Migration and invasion of transfection HEMECs were detected by Transwell assay. The specific experimental procedures refer to the research of Zhou et al [ 23 ]. All samples were run in triplicate.…”

M2 Macrophage-Derived Exosomal lncRNA MIR4435-2HG Promotes Progression of Infantile Hemangiomas by Targeting HNRNPA1

“…LncRNA-TUG1 promotes the proliferation, migration, and invasion of HemECs by regulating the miR-137/IGFBP5 axis. 28 Silencing MALAT1 significantly inhibits the proliferation, migration, and angiogenesis of HemECs, but promotes apoptosis. 29 MIR4435- 2HG participates in the progression of several human diseases and interacts with DNA, RNA, or proteins to regulate transcription, epigenetic modifications, protein/RNA stability, translation, and post-translational modifications.…”

Insulin-like growth factor binding protein 5: Diverse roles in cancer

“…Studies demonstrated that IGFBP5 overexpression abrogated the miR-204-5p induced decrease in cell viability and colony formation, and reversed miR-204-5p induced apoptosis, indicating that miR-204-5p could be acting as a tumor suppressor through its downregulation of IGFBP5 ( 94 ). In infantile hemangioma, miR-137 was found to regulate IGFBP5 expression, and this signaling axis is under the control of the long-noncoding RNA taurine upregulated gene 1 (TUG1) ( 104 ). TUG1 knockdown resulted in increased miR-137, which decreased expression of IGFBP5, and inhibited tumorigenesis in vivo , indicating that TUG1 acts in an oncogenic manner potentially through the upregulation of IGFBP5 ( 104 ).…”

“…In infantile hemangioma, miR-137 was found to regulate IGFBP5 expression, and this signaling axis is under the control of the long-noncoding RNA taurine upregulated gene 1 (TUG1) ( 104 ). TUG1 knockdown resulted in increased miR-137, which decreased expression of IGFBP5, and inhibited tumorigenesis in vivo , indicating that TUG1 acts in an oncogenic manner potentially through the upregulation of IGFBP5 ( 104 ).…”