Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (6): 1-9.doi: 10.6040/j.issn.1671-7554.0.2021.1359

   

LncRNA-HOTAIR regulates migration of macrophages via H3K27me3 pathway

LIU Yan, ZHANG Man, JIANG Chaoyang, BIAN Shu, DU Aijia, CHEN He   

  1. Department of Cardiology, Central Hospital of Shenyang Medical College, Shenyang 110024, Liaoning, China
  • Published:2022-06-17

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Abstract: Objective To explore the expressions of HOX transcribed antisense RNA(LncRNA-HOTAIR)and histone H3 lysine trimethylation at position 27(H3K27me3)in a macrophage model exposed to oxidized low density lipoprotein(oxLDL), and to explore the specific mechanism of HOTAIR regulating H3K27me3 on macrophage migration at the level of gene epigenetics. Methods RAW264.7 macrophages were cultured in vitro, and exposed to oxLDL to prepare the model. The cells were then divided into control group(group A), oxLDL group(group B), macrophage+histone demethylase inhibitor GSKJ4+oxLDL group(group C), macrophage+ histone A GSK126 + oxLDL group(group D), macrophage+oe-HOTAIR+oxLDL group(group E), macrophage+pcDNA+oxLDL group(group F), macrophage+oe-HOTAIR+GSKJ4+oxLDL group(group G), macrophage + pcDNA + GSKJ4 + oxLDL group(group H), macrophage + oe-HOTAIR + GSK126 + oxLDL group(group I), and macrophage + pcDNA + GSK126 + oxLDL group(group J). The protein expressions of H3K27me3 and tumor necrosis factor-α(TNF-α)were detected with Western blotting; the expression of HOTAIR was detected with qPCR, and the migration ability was determined with Transwell assay. Results (1)Compared with group A, group B had increased TNF-α expression and migration ability, but decreased HOTAIR and H3K27me3 expressions, which were positively correlated(P<0.01). (2) Compared with group B, group C had increased H3K27me3 expression, decreased TNF-α expression and migration ability (P<0.01), but the HOTAIR expression did not change significantly(P>0.05); compared with group B, group D had decreased H3K27me3 expression, increased TNF-α expression and migration ability(P<0.01), but the HOTAIR expression did not change significantly(P>0.05). (3) Compared with group B, group E had increased HOTAIR and H3K27me3 expressions, but decreased TNF-α expression and migration ability(P<0.01); compared with group B, group F had not significantly changed HOTAIR, H3K27me3 and TNF-α expressions, and migration ability(P>0.05). (4) Compared with group E, group G had unchanged HOTAIR expression(P>0.05), increased H3K27me3 expression, but decreased TNF-α expression and migration ability(P<0.01); compared with group E, group I had unchanged HOTAIR expression(P>0.05), decreased H3K27me3 expression, but increased TNF-α expression and migration ability(P<0.01). Conclusion In the oxLDL-exposed macrophage migration model, the expression of H3K27me3 is reduced, which affects the expression of TNF-α. LncRNA-HOTAIR is an upstream regulatory factor positively related to the expression of H3K27me3. HOTAIR reduces the expression of TNF-α and migration of macrophages via the H3K27me3 pathway.

Key words: Gene epigenetics, Histones, Methylation modification, HOTAIR, Inflammation

CLC Number: 

  • R543.5
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