Arid2-IR downregulates miR-132-3p through methylation to promote LPS-induced ALI in pneumonia

Abstract

Objective

Arid2-IR is a long non-coding RNA (lncRNA) that promotes renal injury, while its role in lipopolysaccharides (LPS)-induced acute lung injury (ALI) is unknown. Our preliminary sequencing analysis revealed an inverse correlation of Arid2-IR and miR-132-3p, which is known to suppress LPS-induced ALI. Therefore, Arid2-IR and miR-132-3p may interact with each other to participate in LPS-induced ALI in pneumonia. This study aimed to investigate the interaction between Arid2-IR and miR-132-3p in ALI induced by pneumonia.

Materials and methods

Plasma samples were obtained from patients with pneumonia (n = 98) and healthy controls (n = 98) to detect the expression of circulating Arid2-IR and miR-132-3p. The correlation between them was analyzed using Pearson’s correlation coefficient. The crosstalk between them in human bronchial epithelial cells (HBEpC) was analyzed through overexpression assay. MSP was applied to determine the methylation of the miR-132-3p gene. Cell viability was evaluated by 2,5-diphenyl-2H-tetrazolium bromide assay.

Results

Arid2-IR was highly upregulated in pneumonia group, while the expression levels of miR-132-3p decreased in pneumonia group compared to that in the controls. Arid2-IR and miR-132-3p were inversely correlated across patient samples. Overexpression of Arid2-IR decreased the expression levels of miR-132-3p in HBEpCs and increased the methylation of miR-132-3p gene. Arid2-IR suppressed the role of miR-132-3p in increasing the viability of HBEpCs induced by LPS.

Discussion and conclusion

Arid2-IR is upregulated in pneumonia and may downregulate miR-132-3p by increasing its methylation to decrease cell viability, thereby promoting LPS-induced ALI in pneumonia.

Keywords:

• Pneumonia
• LPS-induced acute lung injury
• Arid2-IR
• miR-132-3p

Acknowledgements

The authors thank the financial support from Hainan Health Industry Scientific Research Project, (20A200340).

Ethical approval and consent to participate

All patients signed the written informed consent. All procedures were approved by Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University Ethics Committee. Procedures operated in this research were completed in keeping with the standards set out in the Announcement of Helsinki and laboratory guidelines of research in China.

Author contributions

Yuanshui Liu, Chuanyu Bao, and Yanhong Ouyang contributed to concept, manuscript writing, editing, and review. Gongping Deng contributed to data collection and analysis and manuscript preparation. All authors have read and approve the submission of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was funded by the Hainan Health Industry Scientific Research Project (20A200340).