1. Academic Validation
  2. LncRNA MALAT1 promotes wound healing via regulating miR-141-3p/ZNF217 axis

LncRNA MALAT1 promotes wound healing via regulating miR-141-3p/ZNF217 axis

  • Regen Ther. 2020 Oct 16;15:202-209. doi: 10.1016/j.reth.2020.09.006.
Zun-Hong Liang 1 Yun-Chuan Pan 2 Shi-Shuai Lin 2 Zhi-Yang Qiu 2 Zhi Zhang 1
Affiliations

Affiliations

  • 1 Department of Burn Plastic Surgery, Guangzhou Red Cross Hospital Affiliated to Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
  • 2 Department of Burn Plastic Surgery, Hainan People's Hospital, Haikou, 570311, Hainan Province, PR China.
Abstract

Background: The process of wound healing is complex. Increasing evidences have shown that lncRNA MALAT1 is abundant in fibroblasts and may be engaged in wound healing process. Therefore, we explored the mechanism of MALAT1 affecting wound healing.

Methods: The expression levels of MALAT1, miR-141-3p as well as ZNF217 in human fibroblast cells (HFF-1) were quantified by qRT-PCR. HFF-1 proliferation was measured by MTT, while migration was detected by wound healing assay. SMAD2 activation and matrix proteins expression were detected by western blotting. The interaction between miR-141-3p and MALAT1 or ZNF217 was further confirmed using the luciferase reporter gene assay. In vivo wound healing was assessed by full-thickness wound healing model on C57BL/6 mice.

Result: Knockdown of MALAT1 as well as overexpression miR-141-3p remarkably inhibited the proliferation, migration and matrix protein expression in HFF-1 cells. MALAT1 directly targeted and inhibited the expression of miR-141-3p. MiR-141-3p suppressed the activation of TGF-β2/SMAD2 signaling pathway by targeting ZNF217. Knockdown of MALAT1 inhibited wound healing process in mice.

Conclusions: MALAT1 up-regulates ZNF217 expression by targeting miR-141-3p, thus enhances the activity of TGF-β2/SMAD2 signaling pathway and promotes wound healing process. This investigation shed new LIGHT on the understanding of the role of MALAT1 in wound healing, and may provide potential target for the diagnosis or therapy of chronic wounds.

Keywords

ECM, extra cellular matrix; ELISA, enzyme linked immunosorbent assay; EMT, epithelial mesenchymal transition; HFF-1, human fibroblast cells; MALAT1; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; PVDF, polyvinylidene fluoride; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TGF-β2, Transforming Growth Factor-β2; Wound healing; ZEB1, E-box binding homeobox 1; ZNF217; ZNF217, zinc-finger protein 217; lncRNA, long non-coding RNA; miR-141-3p; qRT-PCR, quantitative real-time PCR.

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