Department of Plastic Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Suzhou, 215004, Jiangsu Province, People's Republic of China.
Department of Orthopedics, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong Province, People's Republic of China.
Mol Cell Biochem. 2021 Aug;476(8):3009-3020. doi: 10.1007/s11010-021-04142-0. Epub 2021 Mar 31.
Hypertrophic Scar (HS) is a complicated fibrotic disease. In addition, its pathogenesis is still to be further explored. Long non-coding RNAs (lncRNAs) have been proved to be participated in multiple diseases, including HS. However, the role of lncRNA TUG1 in HS remains unclear. The expression level of RNA and protein in cells were detected by q-PCR and western blot, respectively. MTT assay was performed to test the cell proliferation. Cell migration was detected by transwell assay. Cell apoptosis was measured by flow cytometry. Dual luciferase report assay and RNA pull down were used to verify the relationship between TUG1, miR-27b-3p and TAK1.TUG1 and TAK1 were upregulated in HS, while miR-27b-3p was downregulated. Knockdown of TUG1 significantly suppressed the proliferation and migration and induced the apoptosis of HS fibroblasts (HSF). In addition, silencing of TUG1 notably inhibited the extracellular matrix (ECM) biosynthesis in HSF. Overexpression of miR-27b-3p has the same effect on HS as that of TUG1 knockdown. Meanwhile, TUG1 could sponge miR-27b-3p, and TAK1 was the direct target of miR-27b-3p. Furthermore, knockdown of TUG1 significantly suppressed the fibrosis in HS via miR-27b-3p/TAK1/YAP/TAZ axis mediation. LncRNA TUG1 promotes the fibrosis in HS via sponging miR-27b-3p and then activates TAK1/YAP/TAZ pathway, which may serve as a potential target for treatment of HS.
增生性瘢痕（HS）是一种复杂的纤维化疾病。此外，其发病机制仍有待进一步探讨。长链非编码 RNA（lncRNA）已被证明参与多种疾病，包括 HS。然而，lncRNA TUG1 在 HS 中的作用尚不清楚。通过 q-PCR 和 Western blot 分别检测细胞中 RNA 和蛋白质的表达水平。MTT 法检测细胞增殖。Transwell 检测细胞迁移。流式细胞术检测细胞凋亡。双荧光素酶报告实验和 RNA 下拉实验验证 TUG1、miR-27b-3p 和 TAK1 之间的关系。TUG1 和 TAK1 在 HS 中上调，而 miR-27b-3p 下调。敲低 TUG1 显著抑制 HS 成纤维细胞（HSF）的增殖和迁移，并诱导其凋亡。此外，沉默 TUG1 显著抑制 HSF 中细胞外基质（ECM）的合成。过表达 miR-27b-3p 对 HS 的作用与 TUG1 敲低相同。同时，TUG1 可以海绵 miR-27b-3p，TAK1 是 miR-27b-3p 的直接靶标。此外，敲低 TUG1 通过 miR-27b-3p/TAK1/YAP/TAZ 轴抑制 HS 中的纤维化。LncRNA TUG1 通过海绵 miR-27b-3p 促进 HS 纤维化，进而激活 TAK1/YAP/TAZ 通路，可能成为治疗 HS 的潜在靶点。
