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Decreased expression of microRNA-145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX-9.

Abstract：

:The present study aimed to determine the expression of microRNA (miRNA or miR)-145 in hypertrophic scars at the tissue and cellular levels, and to investigate its biological functions and mechanism of action. A total of 36 patients who were diagnosed with hypertrophic scar were included in the present study. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of miR-145 in tissues and fibroblasts. Primary fibroblasts were transfected with negative control miRNA, miR-145 mimics or inhibitor. A Cell Counting Kit-8 assay was performed to determine the level of proliferation of fibroblasts. Flow cytometry was employed for cell cycles determination and apoptosis in fibroblasts. A Matrigel assay was used to evaluate the invasion ability of fibroblasts. Western blotting was used to determine the expression of the transcription factor SOX-9 (SOX-9) protein in fibroblasts. Rescue experiments were performed to examine the effect of SOX-9 on the regulation of fibroblasts by miR-145. The dual luciferase reporter assay was performed to identify the direct interaction between SOX-9 and miR-145. The expression of miR-145 was reduced in hypertrophic tissues and fibroblasts. Overexpression of miR-145 inhibited the proliferation, G1/S phase transition and invasion of fibroblasts, and promoted the apoptosis of fibroblasts. In addition, overexpression of miR-145 inhibited SOX-9 protein expression. By contrast, the expression of SOX-9 reversed the effects of miR-145 on the proliferation, cell cycle, apoptosis and invasion of fibroblasts. The miR-145 seed region was able to bind with the 3'-untranslated region of the SOX-9 mRNA to regulate its expression. The present study demonstrated that miR-145 expression is reduced in hypertrophic scar tissues and negatively associated with SOX-9 expression. In addition, miR-145 inhibits the proliferation, cell cycle and invasion, and promotes the apoptosis of fibroblasts by down-regulating the expression of SOX-9. The current study provides a potential target for the clinical diagnosis and treatment of hypertrophic scars.

journal_name

Exp Ther Med

journal_title

Experimental and therapeutic medicine

authors

Wang S,Li C,Yu Y,Qiao J

doi

10.3892/etm.2019.7972

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

3450-3460

issue

eissn

1792-0981

issn

1792-1015

pii

ETM-0-0-7972

journal_volume

pub_type

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Decreased expression of microRNA-145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX-9.