2. Academic Validation
  3. RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1

RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1

  • BMC Mol Cell Biol. 2022 Dec 7;23(1):52. doi: 10.1186/s12860-022-00451-4.
Hanye Liu # 1 2,  Guanghai Yan # 1 2,  Li Li 1 2,  Dandan Wang 1 2,  Yu Wang 1 3,  Shan Jin 1 3,  Zhehu Jin 1 3,  Liangchang Li 4 5,  Lianhua Zhu 6 7
Affiliations

Affiliations

  • 1 Jilin Key Laboratory for Immune and Targeting Research On Common Allergic Diseases, Yanbian University, Yanji, 133000, People's Republic of China.
  • 2 Department of Anatomy, Histology and Embryology, Medical College, Yanbian University, No. 977 Gongyuan Road, Yanji, 133002, People's Republic of China.
  • 3 Department of Dermatology, Yanbian University Hospital, Yanji, 133002, People's Republic of China.
  • 4 Jilin Key Laboratory for Immune and Targeting Research On Common Allergic Diseases, Yanbian University, Yanji, 133000, People's Republic of China. [email protected].
  • 5 Department of Anatomy, Histology and Embryology, Medical College, Yanbian University, No. 977 Gongyuan Road, Yanji, 133002, People's Republic of China. [email protected].
  • 6 Jilin Key Laboratory for Immune and Targeting Research On Common Allergic Diseases, Yanbian University, Yanji, 133000, People's Republic of China. [email protected].
  • 7 Department of Dermatology, Yanbian University Hospital, Yanji, 133002, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 36476345 DOI: 10.1186/s12860-022-00451-4
Abstract

Background: Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)/ Zeste Homolog 2 (EZH2)/ Runt-related transcription factor 3 (RUNX3). METHODS: HE staining was used to observe the histopathological changes. Western blot was performed to detect SIRT1/EZH2/RUNX3 and cell cycle related proteins. RT-PCR detected EZH2 mRNA. After knockdown of EZH2 or overexpression of RUNX3, cell proliferation and cell cycle was analyzed. Immunoprecipitation was used to detect acetylated EZH2.

Results: The results showed that overexpression of RUNX3 inhibited cell proliferation and arrested cell cycle at G1/S phase, whereas inhibition of SIRT1 promoted cell proliferation and G1/S phase of the cell cycle. Knockdown of EZH2 promoted the expression of RUNX3, inhibited cell proliferation and shortened the progression of G1 to S phase. Simultaneous knockdown of EZH2 and inhibition of SIRT1 reversed these effects. Inhibition of SIRT1 increased its protein stability by increasing EZH2 acetylation, thereby reducing the expression of RUNX3 and promoting cell proliferation.

Conclusions: Conclusively, the SIRT1/EZH2/RUNX3 axis may be an important pathway in the regulation of abnormal proliferation in keloids.

Keywords

Abnormal proliferation; Cell cycle; Keloid; SIRT1/EZH2/RUNX3 axis.

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