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hsa_circ_0037722 通过与 miR-140-3p 和 NR2F2 相互作用驱动瘢痕疙瘩形成。

hsa_circ_0037722 Drives Keloid Formation by Interacting with miR-140-3p and NR2F2.

机构信息

Department of Plastic Surgery, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430000, Hubei, China.

Wound Repair & Rehabilitation Center, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430000, Hubei, China.

出版信息

Crit Rev Immunol. 2024;44(1):17-29. doi: 10.1615/CritRevImmunol.2023050332.

Abstract

Keloids can invade normal skin tissues to lead to itching, pain, hemorrhaging and suppuration, thereby affecting the mental health of patients. circRNAs can participate in keloids formation, but the role of hsa_circ_0037722 in keloids is still unknown. The goal of our study was to reveal the role of hsa_circ_0037722 in keloids. The levels of hsa_circ_0037722, miR-140-3p and NR2F2 in keloids was confirmed by qRT-PCR. Cell experiments were applied to assess the effect of hsa_circ_0037722/miR-140-3p/NR2F2 axis on keloids formation. In addition, the correlation among hsa_circ_0037722, miR-140-3p and NR2F2 was confirmed by luciferase assay. hsa_circ_0037722 and NR2F2 were upregulated in keloids tissues and keloids fibroblasts, whereas miR-140-3p was downregulated in keloids tissues and keloids fibroblasts. The abilities of proliferation and metastasis of keloids fibroblasts were impaired by silencing hsa_circ_0037722. However, miR-140-3p inhibitor or NR2F2 overexpression could restore the inhibitory function of hsa_circ_0037722 knockdown in keloid fibroblasts due to their targeting relationship. Taken together, hsa_circ_0037722 can facilitate keloids formation by interacting with miR-140-3p to relieve the suppression of miR-140-3p for NR2F2. The findings of this study may provide a novel idea for developing molecular targeted therapies for keloid.

摘要

瘢痕疙瘩可侵犯正常皮肤组织,导致瘙痒、疼痛、出血和化脓,从而影响患者的心理健康。circRNAs 可参与瘢痕疙瘩的形成,但 hsa_circ_0037722 在瘢痕疙瘩中的作用尚不清楚。本研究旨在揭示 hsa_circ_0037722 在瘢痕疙瘩中的作用。通过 qRT-PCR 证实了瘢痕疙瘩中 hsa_circ_0037722、miR-140-3p 和 NR2F2 的水平。应用细胞实验评估了 hsa_circ_0037722/miR-140-3p/NR2F2 轴对瘢痕疙瘩形成的影响。此外,通过荧光素酶测定证实了 hsa_circ_0037722、miR-140-3p 和 NR2F2 之间的相关性。hsa_circ_0037722 和 NR2F2 在瘢痕疙瘩组织和瘢痕疙瘩成纤维细胞中上调,而 miR-140-3p 在瘢痕疙瘩组织和瘢痕疙瘩成纤维细胞中下调。沉默 hsa_circ_0037722 可抑制瘢痕疙瘩成纤维细胞的增殖和转移能力。然而,由于 miR-140-3p 抑制剂或 NR2F2 过表达可靶向作用 hsa_circ_0037722 抑制物,从而恢复了 hsa_circ_0037722 敲低对瘢痕疙瘩成纤维细胞的抑制功能。总之,hsa_circ_0037722 可通过与 miR-140-3p 相互作用促进瘢痕疙瘩形成,从而缓解 miR-140-3p 对 NR2F2 的抑制作用。本研究结果可为瘢痕疙瘩的分子靶向治疗提供新的思路。

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