LncRNA H19 aggravates TNF‐α‐induced inflammatory injury via TAK1 pathway in MH7A cells

Abstract

Rheumatoid arthritis (RA) is a common chronic autoimmune disease in women. This research aims to disclose the probable function of lncRNA H19 in MH7A cells. The influences of tumor necrosis factor-α (TNF-α) on cell viability, apoptosis, and inflammatory factor expression were, respectively, detected through cell counting kit-8 (CCK-8), flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) assay and Western Blot. The levels of H19 and TAK1 were, respectively, tested through qRT-PCR and Western blot. The expression of NF-κB and JNK/p38MAPK pathway-associated proteins was tested through Western blot. We found that TNF-α reduced MH7A cell viability in a concentrationdependent manner and facilitated apoptosis and IL-8, IL-1β, and IL-6 production. Besides, TNF-α treatment raised the level of H19 in MH7A cells. Moreover, H19 silence reduced the levels of inflammatory cytokines, while overexpression of H19 reversed this effect. TNF-α treatment elevated the expression of inflammatory cytokines by up-regulating H19. Furthermore, overexpression of H19 promoted TAK1 phosphorylation. Following studies revealed that H19 activated NF-κB and JNK/p38 MAPK pathways by promoting TAK1 phosphorylation.

Current situation and trend of non-coding RNA in rheumatoid arthritis: a review and bibliometric analysis

“…Overexpression of H19 in PMA-induced THP-1 cells (a common model used to study macrophage activity modulation) upregulates KDM6A and various M1 macrophage-associated factors (particularly CCL8, CXCL9, CXCL10, and CXCL11) which promote M1 macrophage activity and macrophage migration ( 186 ). LncRNA H19 can also aggravate TNF-α-induced inflammatory injury via TAK1 pathway in MH7A cells ( 41 ). LncRNA Hotair exhibited notably high expression levels in the PBMCs and serum exosomes of RA patients, promoting the migration of activated macrophages ( 187 ).…”

Long Non-Coding RNAs in Colorectal Cancer: Navigating the Intersections of Immunity, Intercellular Communication, and Therapeutic Potential

“…Moreover, H19 is involved in the STAT3 pathway, which is critical for cancer aggressiveness, potentially impacting the tumor microenvironment. Therefore, the examination of H19 in the context of CRC could yield valuable insights into tumorigenesis, inflammation, and potential therapeutic strategies [ 105 , 106 , 107 ].…”

Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets

“…Both the MAP kinase ERK-1/2 pathway and the phosphatidylinositol 3-kinase pathway affected the H19 RNA expression. The increased sensitivity of overexpressed H19 RNA to starvation/cytokine regulation in RA indicated that embryo genes were involved in the pathogenesis of RA, which reflect the embryonic dedifferentiation and continuous inflammation in synovial tissue (Stuhlmüller et al, 2003;Jarroux et al, 2017;Yang et al, 2020).…”