Yuanbin Zhu1, Yingying Wang1, Shigang Xing1, Jie Xiong2. 1. Department of Respiratory, Linyi Central Hospital, Linyi, Shandong, China. 2. Department of Respiratory, Linyi Central Hospital, Linyi, Shandong, China. Electronic address: zmg76mt@163.com.
Abstract
BACKGROUND: Emerging evidence show that long noncoding RNAs (lncRNAs) are crucial regulators in pathophysiology of acute lung injury (ALI). Small nucleolar RNA host gene 14 (SNHG14) is a novel oncogenic lncRNA, and has been associated with inflammation-related cell injuries. Thus, we wondered the role and mechanism of SNHG14 in lipopolysaccharides (LPS)-induced ALI cell model. METHODS: Expression of SNHG14, miRNA (miR)-124-3p, and transforming growth factor β type 2 receptor (TGFBR2) was detected by RT-qPCR and western blotting. Cell apoptosis was determined by methyl thiazolyl tetrazolium assay, flow cytometry, western blotting, and lactate dehydrogenase activity kit. Inflammation was measured by enzyme-linked immunosorbent assay. The interaction among SNHG14, miR-124-3p, and TGFBR2 was validated by dual-luciferase reporter assay and RNA immunoprecipitation. RESULTS: LPS administration attenuated human lung epithelial cell viability and B-cell lymphoma-2 expression, but augmented apoptosis rate, cleaved-caspase-3 expression, lactate dehydrogenase activity, and secretions of tumor necrosis factor-α, interleukin-1β, and IL-6 in A549 cells. Thus, LPS induced A549 cells apoptosis and inflammation, wherein SNHG14 was upregulated and miR-124-3p was downregulated. However, silencing SNHG14 could suppress LPS-induced apoptosis and inflammation depending on upregulating miR-124-3p via target binding. Similarly, overexpressing miR-124-3p attenuated LPS-induced A549 cells injury through inhibiting its downstream target TGFBR2. Furthermore, SNHG14 knockdown could also affect TGFBR2 expression via miR-124-3p. CONCLUSIONS: SNHG14 knockdown prevents A549 cells from LPS-induced apoptosis and inflammation through regulating miR-124-3p and TGFBR2, suggesting a novel SNHG14/miR-124-3p/TGFBR2 circuit in alveolar epithelial cells on the set of ALI.
BACKGROUND: Emerging evidence show that long noncoding RNAs (lncRNAs) are crucial regulators in pathophysiology of acute lung injury (ALI). Small nucleolar RNA host gene 14 (SNHG14) is a novel oncogenic lncRNA, and has been associated with inflammation-related cell injuries. Thus, we wondered the role and mechanism of SNHG14 in lipopolysaccharides (LPS)-induced ALI cell model. METHODS: Expression of SNHG14, miRNA (miR)-124-3p, and transforming growth factor β type 2 receptor (TGFBR2) was detected by RT-qPCR and western blotting. Cell apoptosis was determined by methyl thiazolyl tetrazolium assay, flow cytometry, western blotting, and lactate dehydrogenase activity kit. Inflammation was measured by enzyme-linked immunosorbent assay. The interaction among SNHG14, miR-124-3p, and TGFBR2 was validated by dual-luciferase reporter assay and RNA immunoprecipitation. RESULTS:LPS administration attenuated human lung epithelial cell viability and B-cell lymphoma-2 expression, but augmented apoptosis rate, cleaved-caspase-3 expression, lactate dehydrogenase activity, and secretions of tumor necrosis factor-α, interleukin-1β, and IL-6 in A549 cells. Thus, LPS induced A549 cells apoptosis and inflammation, wherein SNHG14 was upregulated and miR-124-3p was downregulated. However, silencing SNHG14 could suppress LPS-induced apoptosis and inflammation depending on upregulating miR-124-3p via target binding. Similarly, overexpressing miR-124-3p attenuated LPS-induced A549 cells injury through inhibiting its downstream target TGFBR2. Furthermore, SNHG14 knockdown could also affect TGFBR2 expression via miR-124-3p. CONCLUSIONS:SNHG14 knockdown prevents A549 cells from LPS-induced apoptosis and inflammation through regulating miR-124-3p and TGFBR2, suggesting a novel SNHG14/miR-124-3p/TGFBR2 circuit in alveolar epithelial cells on the set of ALI.
Authors: Bo Zhang; Qing Zhang; Linying Yang; Hongfei Zheng; Guifen Pang; Mingzhen Zhao; Bo Sun; Jie Cao Journal: Evid Based Complement Alternat Med Date: 2022-04-11 Impact factor: 2.650