Tanshinone IIA protects motor neuron-like NSC-34 cells against lipopolysaccharide-induced cell injury by the regulation of the lncRNA TCTN2/miR-125a-5p/DUSP1 axis

Qiwen Yan; Yajing Xun; Debao Lei; Hongyu Zhai

doi:10.1016/j.reth.2023.03.007

Tanshinone IIA protects motor neuron-like NSC-34 cells against lipopolysaccharide-induced cell injury by the regulation of the lncRNA TCTN2/miR-125a-5p/DUSP1 axis

Regen Ther. 2023 Sep 13:24:417-425. doi: 10.1016/j.reth.2023.03.007. eCollection 2023 Dec.

Authors

Qiwen Yan¹, Yajing Xun¹, Debao Lei¹, Hongyu Zhai¹

Affiliation

¹ Department of Rehabilitation Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang City, 441000, Hubei, China.

Abstract

Background: Tanshinone IIA (TSIIA) exerts a protective role in spinal cord injury (SCI). However, the mechanism of TSIIA activity in SCI remains to be elucidated.

Methods: Cell viability and apoptosis were gauged by CCK-8 assay and flow cytometry, respectively. The expression levels of lncRNA TCTN2, miR-125a-5p and DUSP1 were detected by qRT-PCR and western blot. Direct relationship between miR-125a-5p and TCTN2 or DUSP1 was verified by dual-luciferase reporter assay.

Results: In mouse NSC-34 cells, LPS reduced the expression of TCTN2. TSIIA alleviated cell injury induced by LPS and increased TCTN2 expression in LPS-exposed NSC-34 cells. TCTN2 was a downstream mediator of TSIIA activity. TCTN2 targeted miR-125a-5p, and TCTN2 over-expression attenuated LPS-induced cell damage in NSC-34 cells by down-regulating miR-125a-5p. TCTN2 functioned as a post-transcriptional regulator of DUSP1 expression through miR-125a-5p. DUSP1 was a functional target of miR-125a-5p in controlling NSC-34 cell injury induced by LPS. TSIIA inhibited miR-125a-5p expression and increased the level of DUSP1 protein in LPS-exposed NSC-34 cells.

Conclusion: Our study establishes a novel mechanism, the TCTN2/miR-125a-5p/DUSP1 axis, at least in part, for the protective activity of TSIIA in cell injury induced by LPS.

Keywords: Cell injury; DUSP1; TCTN2; Tanshinone IIA; miR-125a-5p.