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LncRNA TUG1 exhibits pro-fibrosis activity in hypertrophic scar through TAK1/YAP/TAZ pathway via miR-27b-3p

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Abstract

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.

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Abbreviations

TAK1:

TGF-β-activated kinase-1

YAP:

Yes-activated protein

TAZ:

Traffic analysis zones

TUG1:

Taurine-upregulated gene 1

HS:

Hypertrophic scar

NS:

Normal skin

HSF:

HS fibroblasts

NSF:

NS fibroblasts

collagen I:

COL1A1

collagen III:

COL3A1

fibronectin 1:

FN1

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Authors and Affiliations

  1. Department of Plastic Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Suzhou, 215004, Jiangsu Province, People’s Republic of China

    Xian-Min Li, Wen-Yuan Yu, Qi Chen, Hui-Ru Zhuang, Su-Yue Gao & Tian-Lan Zhao

  2. Department of Orthopedics, Gaozhou People’s Hospital, Gaozhou, 525200, Guangdong Province, People’s Republic of China

    Xian-Min Li

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  1. Xian-Min Li
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Contributions

guarantor of integrity of the entire study: T-LZ; study concepts: X-ML; study design: X-ML, T-LZ; definition of intellectual content: W-YY, QC; literature research: H-RZ, S-YG; experimental studies: X-ML, W-YY; data acquisition: X-ML, T-LZ, QC; data analysis: X-ML, H-Ru Zhuang; statistical analysis: X-ML, H-RZ; manuscript preparation: X-ML, T-LZ; manuscript editing X-ML, S-YG; manuscript review: T-LZ.

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Correspondence to Tian-Lan Zhao.

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Li, XM., Yu, WY., Chen, Q. et al. LncRNA TUG1 exhibits pro-fibrosis activity in hypertrophic scar through TAK1/YAP/TAZ pathway via miR-27b-3p. Mol Cell Biochem 476, 3009–3020 (2021). https://doi.org/10.1007/s11010-021-04142-0

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