Pre-B cell leukemia transcription factor 3 induces inflammatory responses in human umbilical vein endothelial cells and murine sepsis via acting a competing endogenous RNA for high mobility group box 1 protein

• Published in: Molecular medicine reports Vol. 17; no. 4; pp. 5805 - 5813
• Main Authors: Zhang, Yunzhong, Feng, Jing, Cui, Jizhen, Yang, Guozheng, Zhu, Xianai
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.04.2018; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: 3' Untranslated regions; Abdomen; Analysis; Breast cancer; Cecum; Complications and side effects; Construction; Endothelial cells; Genes; Genetic aspects; Health aspects; High mobility group proteins; HMGB1 protein; Inflammation; Interleukin 6; Kinases; Leukemia; Leukocyte migration; Lipopolysaccharides; Lymphocytes B; MicroRNA; MicroRNAs; miRNA; Mobility; Mortality; Physiological aspects; Plasmids; Polymerase chain reaction; Proteins; Reverse transcription; Rodents; Sepsis; siRNA; Studies; Transcription factors; Tumor necrosis factor-TNF; Umbilical vein; China; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2018.8609

The present study investigated the roles of pre-B cell leukemia transcription factor 3 (PBX3) in sepsis. Reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that overexpression of the PBX 3'‑untranslated region (UTR) promoted high mobility group box 1 (HMGB1) protein expression in human umbilical vein endothelial cells (HUVECs) (P<0.01). Furthermore, post‑treatment of PBX3 small interfering (si)RNA suppressed lipopolysaccharide (LPS)‑mediated HMGB1 release and attenuated HMGB1‑mediated hyperpermeability and leukocyte migration in HUVECs and septic mice (P<0.01). Additionally, post‑injection of PBX3 siRNA also induced the downregulation of cecal ligation and puncture‑induced HMGB1 release, production of IL‑6 and mortality (P<0.01). Mechanistically, the 3'UTRs of PBX3 and HMGB1 were identified to harbor six common micro (mi)RNA binding sites, and PBX 3'UTR increased HMGB1 expression in a 3'UTR‑ and miRNA‑dependent manner. Notably, the coding sequence of PBX3 did not increase HMGB1 expression in HUVECs. Collectively, the present study indicates that PBX 3'UTR may induce inflammatory responses and sepsis via acting as a competing endogenous RNA for HMGB1.