Circ_0038467 regulates lipopolysaccharide‐induced inflammatory injury in human bronchial epithelial cells through sponging miR‐338‐3p

Abstract

Background: Pneumonia is a common acute lower respiratory infection in children and elders. Circular RNAs (circRNAs) have recently been uncovered to play important roles in pneumonia. However, the function and mechanism of circ_0038467 in pneumonia remain elusive. Methods: Cell viability and apoptosis were determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The levels of interleukin 6 (IL-6), IL-8 and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to assess the expression of related proteins. Circ_0038467 was characterized by Ribonuclease R (RNase) digestion and subcellular localization assays. The levels of circ_0038467 and miR-338-3p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The direct interaction between circ_0038467 and miR-338-3p was validated by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: Our data indicated that lipopolysaccharide (LPS) induced an inflammatory injury in 16HBE cells by repressing cell viability and enhancing cell apoptosis and proinflammatory cytokines production. Circ_0038467 was upregulated and miR-338-3p was downregulated in LPS-treated 16HBE cells. Circ_0038467 knockdown or miR-338-3p overexpression attenuated LPS-induced 16HBE cell inflammatory injury. Moreover, circ_0038467 acted as a sponge of miR-338-3p in 16HBE cells. MiR-338-3p mediated the alleviated effect of circ_0038467 knockdown on LPS-induced 16HBE cell inflammatory injury. Additionally, the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was involved in the circ_0038467/miR-338-3p axis-mediated regulation in LPS-induced 16HBE cell inflammatory injury. Conclusions: The current work had led to the identification of circ_0038467 knockdown that alleviated LPS-induced inflammatory injury in 16HBE cells at least partly through sponging miR-338-3p and regulating JAK/STAT3 pathway, highlighting novel molecular targets for the treatment of pneumonia.

Circ_0038467 is Overexpressed in Osteoarthritis and it Promotes the Maturation of miR-203 to Increase the Apoptosis of Chondrocytes Induced by LPS

“…Liu et al reported that Circ_0038467 was upregulated in human bronchial epithelial cells by LPS treatment and the knockdown of Circ_0038467 protected cells from LPS-induced injury (15), suggesting that Circ_0038467 may promote LPS-induce cell injury. Consistently, our study also showed that LPS treatment increased the expression of Circ_0038467 in chondrocytes in a dose-dependent manner.…”

“…In OA, CircRNAs not only participates in disease progression, but also serves as biomarkers for disease diagnosis and prognosis (13), suggesting the potential roles of circRNAs as promising targets for OA targeted therapy. The development of osteoarthritis (OA) requires the involvement of LPS-induced in ammation (14), in which circRNA Circ_0038467 plays a critical role (15), suggesting the involvement of Circ_0038467 in OA. Our deep sequence analysis revealed the altered expression of Circ_0038467 and its inverse correlation with miR-203 (data not shown), which is also a critical player in LPS-induced cell injury (16).…”

let7f‑5p attenuates inflammatory injury in in vitro pneumonia models by targeting MAPK6

“…The STAT3 signaling pathway is pivotal for the inflammatory response ( 31 ). During acute inflammatory injury, the STAT3 signaling pathway is implicated in lung injury ( 32 ) and LPS-induced inflammatory injury, as well as in the circular RNA (circ)_0038467/miR-338-3p axis ( 33 ). The results of the present study demonstrated that LPS significantly increased STAT3 activation compared with the control group, which was reversed by transfection with let7f-5p mimic.…”

Circular RNAs in childhood‐related diseases and cancers: A review

“…circ‐0038467 is postulated to have acted as a sponge of miR‐338‐3p to regulate LPS‐induced inflammatory injury. The JAK/STAT3 signalling pathway appeared to be involved in the regulation of the circ‐0038467/miR‐338‐3p axis 122 . Neodymium oxide (Nd 2 O 3 ) can be used to induce inflammatory damage of 16HBE cells, and the up‐regulated circ‐0039411 is involved in the inflammatory promotion of 16HBE cells by the circ‐0039411/miR‐93‐5p/STAT3 pathway 123 .…”