Long Noncoding RNA (lncRNA) Maternally Expressed Gene 3 (MEG3) Participates in Chronic Obstructive Pulmonary Disease through Regulating Human Pulmonary Microvascular Endothelial Cell Apoptosis

Abstract

Background:Chronic obstructive pulmonary disease (COPD), a general airway disease, is featured by progressive and chronic immunoreaction in the lung. Increasing evidences have showed that cigarette smoking is the main reason in the COPD progression, and human pulmonary microvascular endothelial cell (HPMEC) apoptosis often be observed in COPD, while its pathogenesis is not yet fully described. Upregulation of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) was observed in COPD patients, but the specific mechanism of lncRNA MEG3 in COPD remains unknown. The objective of this research was to explore the role of lncRNA MEG3 in cigarette smoke extract (CSE)-induced HPMECs. Material/Methods:HPMECs were induced by a series of concentrations of CSE (0%, 0.1%, 1%, and 10%). Then cell apoptosis was analyzed by flow cytometry. Cell apoptosis related proteins were tested using western blot assay. Finally, we applied knockdown and over-expression system to explore the lncRNA MEG3 functions in CSE-induced HPMECs. Results:Our results indicated that various concentrations of CSE (0%, 0.1%, 1%, and 10%) significantly promoted cell apoptosis, augmented caspase-3 activity, upregulated Bax expression, decreased Bcl-2 expression, and enhanced lncRNA MEG3 level in HPMECs. LncRNA MEG3-plasmid transfection resulted in the upregulation of lncRNA MEG3, more apoptotic HPMECs, and higher caspase-3 activity. While lncRNA MEG3 knockdown presented the opposite effects. Further investigation suggested that all the effects of CSE treatment on HPMECs were markedly reversed by lncRNA MEG3-shRNA (short hairpin RNA). Conclusions:Our study illustrated a protective effect of lncRNA MEG3-shRNA on CSE-induced HPMECs, indicting lncRNA MEG3 can be a new therapeutic approach for COPD treatment.

The value of circulating long non‐coding RNA maternally expressed gene 3 as a predictor of higher acute respiratory distress syndrome risk and 28‐day mortality in sepsis patients

“…Preceding researches identified lncRNA MEG3 as a regulator for lung injury through modulating inflammatory signaling pathways or cell apoptosis‐related pathways in multiple inflammatory diseases 8‐11 . As an example, Zou et al unravel that lncRNA MEG3 knockdown attenuates cell damage to subsequently attenuate hyperoxia‐induced lung injury via inhibiting non‐obese diabetic‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity and caspase‐1 signaling 10 .…”

“…As an example, Zou et al unravel that lncRNA MEG3 knockdown attenuates cell damage to subsequently attenuate hyperoxia‐induced lung injury via inhibiting non‐obese diabetic‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity and caspase‐1 signaling 10 . Another study illuminates that lncRNA MEG3 induces pulmonary microvascular endothelial cell apoptosis via the upregulation of caspase‐3 activity, reduction of Bcl‐2 level, and elevation of Bax in chronic obstructive pulmonary disease 11 . Meanwhile, lncRNA MEG3 has a good predictive value for disease risk of respiratory disease asthma 12 .…”

“…As for sepsis‐related ARDS, lncRNA MEG3 was increased in ARDS sepsis patients compared with non‐ARDS sepsis patients, and lncRNA MEG3 exhibited the value for predicting ARDS risk in sepsis patients. These findings were likely to explained by that lncRNA MEG3 might trigger the production of hyperoxia‐induced inflammatory cytokines in lung tissues and facilitate pulmonary microvascular endothelial cell apoptosis/subsequent lung injury by modulating its downstream pathways such as NLRP3 inflammasome‐mediated caspase‐1 pathway, which might contribute to augmented ARDS risk in sepsis patients 10,11 . However, these hypothetical explanations needed further validation.…”

“…6,7 Recent researches reveal that lncRNA MEG3 is involved in the regulation of lung injury through regulating multiple inflammation-relative signaling pathways and apoptosis-related pathways such as caspase-1 signaling and Janus kinases/ signal transducer and activator of transcription proteins. [8][9][10][11] Meanwhile, lncRNA MEG3 exhibited the potential as a biomarker for identifying disease risk and progression of respiratory disease asthma. 12 As for sepsis, lncRNA MEG3 modulates the pulmonary inflammatory responses to affect the initiation and progression of sepsis, and it displays the clinical implication in predicting prognosis in sepsis patients.…”

“…Long non‐coding maternally expressed gene 3 (LncRNA MEG3), located within the imprinted DLK1‐DIO3 gene cluster at chromosome 14q32.3, is initially identified as a lncRNA with the function of tumor suppressor 6,7 . Recent researches reveal that lncRNA MEG3 is involved in the regulation of lung injury through regulating multiple inflammation‐relative signaling pathways and apoptosis‐related pathways such as caspase‐1 signaling and Janus kinases/signal transducer and activator of transcription proteins 8‐11 . Meanwhile, lncRNA MEG3 exhibited the potential as a biomarker for identifying disease risk and progression of respiratory disease asthma 12 .…”