Long noncoding RNA HAGLROS regulates cell apoptosis and autophagy in lipopolysaccharides-induced WI-38 cells via modulating miR-100/NF-κB axis

Abstract

Pneumonia is a lower respiratory disease caused by pathogens or other factors. This study aimed to explore the roles and mechanism of long noncoding RNA HAGLROS in lipopolysaccharides (LPS)-induced inflammatory injury in pneumonia. The HAGLROS expression in serum of patients with acute stage pneumonia was detected. To induce pulmonary injury, WI-38 human lung fibroblasts were stimulated with lipopolysaccharides (LPS). The HAGLROS expressions in LPS-treated WI-38 cells and the effects of HAGLROS knockdown on the viability, apoptosis, and autophagy of LPS-induced cells were detected. Moreover, the regulatory relationship between HAGLROS and miR-100 was explored as well as the functional targets of miR-100 were identified. Furthermore, the regulatory relationship between miR-100 and PI3K/AKT/NF-κB pathway was elucidated. LncRNA HAGLROS was higher expressed in serum of patients with acute stage pneumonia compared with that in serum of healthy control. LPS caused WI-38 cell injury and increased HAGLROS levels. Downregulation of HAGLROS alleviated LPS-induced cell injury via increasing cell viability, and inhibiting apoptosis and autophagy. Moreover, there was a negative correlation between HAGLROS and miR-100, and the effects of HAGLROS downregulation on LPS-induced apoptosis and autophagy in WI-38 cells were by regulation of miR-100. Furthermore, NFΚB3 was verified as a functional target of miR-100 and effects of miR-100 inhibition on LPS-induced WI-38 cell injury were alleviated by knockdown of NFΚB3. Besides, Knockdown of HAGLROS inhibited the activation of PI3K/AKT/NF-κB pathway. Our findings reveal that downregulation of HAGLROS may alleviate LPS-induced inflammatory injury in WI-38 cells via modulating miR-100/NF-κB axis. HAGLROS/miR-100/NF-κB axis may provide a new strategy for treating acute stage of pneumonia.

Knockdown XIST alleviates LPS‐induced WI‐38 cell apoptosis and inflammation injury via targeting miR‐370‐3p/TLR4 in acute pneumonia

“…The release of inflammatory factors, such as TNF‐α, could promote cell apoptosis, microvascular dysfunction, and tissue necrosis . The cumulative message of several recent studies has revealed that lncRNAs are abnormally involved in inflammation response and serve as effective therapeutic targets for pneumonia . We put forward biological functions and mechanisms of XIST in pneumonia and firstly found that XIST knockdown lead to the inhibition of cell apoptosis and inflammation injuries in LPS‐induced WI‐38 cells by sponging miR‐370‐3p.…”

“…Cells (2 × 10 5 ) were plated in 6‐well plates and incubated 24 hours. LPS in different concentrations (5, 10, and 20 μg/mL) was added in medium for 12 hours to establish injury model …”

“…In this study, XIST was detected highly expressed in serum of acute‐stage pneumonia. To verify our hypothesis that whether XIST could regulate pneumonia development, pneumonia and lung injury cell model was constructed by LPS induction in WI‐38 cells as described in some previous studies . Furthermore, knockdown of XIST inhibited the LPS‐induced cell viability, apoptosis, and inflammatory damage.…”

hsa-miR-100-5p, an overexpressed miRNA in human ovarian endometriotic stromal cells, promotes invasion through attenuation of SMARCD1 expression

“…The reported target genes of hsa-miR-100-5p include polo-like kinase 1 [21,32], insulin-like growth factor (IGF) [33], IGF-1 receptor [34], mammallian target of rapamycin (mTOR) [34], fibroblast growth factor receptor 3 [35], ataxia telangiectasia mutated (ATM) [36], Argonaute 2 [37], isoprenylcysteine carboxyl methyltransferase (ICMT) [38], nuclear factor-κB3 [39], rasrelated C3 botulinum toxin substrate 1 (Rac1) [38], and β-tubulin [40].…”

lncRNA GAS5 promotes M1 macrophage polarization via miR‐455‐5p/SOCS3 pathway in childhood pneumonia

“…Long noncoding RNAs (lncRNAs) play critical roles in a variety of human diseases including pneumonia (Huang et al, ; M. Liu, Han, Shi, & Chen, ). LncRNA growth arrest‐specific 5 (GAS5) has been demonstrated to have a role in macrophage polarization (Simion, Haemmig, & Feinberg, ).…”