lncRNA MALAT1 Accelerates Skeletal Muscle Cell Apoptosis and Inflammatory Response in Sepsis by Decreasing BRCA1 Expression by Recruiting EZH2
| Autor: | Gangming Wu, Jicheng Wei, Li Liu, Jingyuan Chen, Hui Yong, Ni Tang, Yiping Bai, Xueru Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
skeletal muscle cells Article sepsis Sepsis 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Gene silencing long non-coding RNA MALAT1 EZH2 MALAT1 business.industry lcsh:RM1-950 apoptosis Skeletal muscle Interleukin Correction inflammatory response BRCA1 medicine.disease lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Cancer research Molecular Medicine Tumor necrosis factor alpha business |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 21, Iss, Pp 1120-1121 (2020) |
| ISSN: | 2162-2531 |
| Popis: | Sepsis is a serious and elusive syndrome caused by infection, which is accompanied by a high mortality worldwide. Recent evidence has documented the regulatory role of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) during the inflammatory process, the effects of which in the development of sepsis have become the focus of the current study. An in vivo mouse model and in vitro cell model of sepsis induced by lipopolysaccharide (LPS) were developed. High expression of lncRNA MALAT1 along with low expression of breast cancer susceptibility gene 1 (BRCA1) were identified in septic mice and human skeletal muscle cells of sepsis. Then, lncRNA MALAT1 expression was altered in vivo and in vitro to examine serum levels of inflammatory factors, as well as skeletal muscle cell apoptosis. lncRNA MALAT1 was noted to regulate the expression and export from the nucleus of BRCA1 by recruiting zeste homolog 2 (EZH2) in skeletal muscle cells of sepsis. Silencing lncRNA MALAT1 resulted in reduced serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), neutrophil migration, skeletal muscle cell apoptosis, and AKT-1 phosphorylation. Taken together, lncRNA MALAT1 interacting with EZH2 stimulated AKT-1 phosphorylation and decreased BRCA1 expression, consequently aggravating the progression of sepsis, highlighting a promising therapeutic option for sepsis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|