hsa_circ_0038382 upregulates T-box transcription factor 5 to inhibit keloid formation by interacting with miR-940

Adv Clin Exp Med. 2023 May;32(5):593-601. doi: 10.17219/acem/155949.

Abstract

Background: A keloid is a benign fibroproliferative skin tumor whose formation is regulated by circular RNAs (circRNAs). However, the effect and regulatory mechanism of hsa_circ_0038382 on keloid formation have not been investigated.

Objectives: This study aimed to identify the function and mechanism of hsa_circ_0038382 in keloid formation.

Material and methods: The expression levels of hsa_circ_0038382, microRNA-940 (miR-940) and T-box transcription factor 5 (TBX5) were measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). After cell transfection of keloid fibroblasts, the effect of the hsa_circ_0038382/miR-940/TBX5 axis on keloid formation was assessed using cell function tools such as the cell counting kit-8 (CCK-8) assay, transwell migration assay and transwell invasion assay. The binding sites among hsa_circ_0038382, miR-940 and TBX5 were predicted with CircInteractome and TargetScan, and further identified using luciferase assays.

Results: The levels of hsa_circ_0038382 and TBX5 were reduced, whereas the level of miR-940 was elevated in keloid samples. Cell function experiments confirmed that hsa_circ_0038382 can inhibit keloid formation by suppressing proliferation, migration and invasion of keloid fibroblasts. Luciferase assays proved that hsa_circ_0038382 can absorb miR-940 to regulate TBX5 expression in keloids. Additionally, the overexpression of TBX5 restored the effect of hsa_circ_0038382 knockdown on keloid fibroblasts.

Conclusions: This study suggests that hsa_circ_0038382 attenuates keloid formation by regulating the miR-940/TBX5 axis, which might provide a potential therapeutic target in the treatment of keloid formation.

Keywords: TBX5; hsa_circ_0038382; keloid; miR-940.

MeSH terms

  • Cell Proliferation
  • Fibroblasts
  • Humans
  • Keloid* / genetics
  • MicroRNAs* / genetics
  • Skin Neoplasms*
  • T-Box Domain Proteins

Substances

  • T-box transcription factor 5
  • T-Box Domain Proteins
  • MicroRNAs
  • MIRN940 microRNA, human