LncRNA CASC2 Alleviates Sepsis-induced Acute Lung Injury by Regulating the miR-152-3p/PDK4 Axis

ABSTRACT

Background

Acute lung injury (ALI) is an early complication of sepsis and it is also considered as an important cause of high mortality in sepsis patients. This research aimed to explore the potential role and mechanism of long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in sepsis-induced ALI.

Methods

The levels of CASC2, microRNA-152-3p (miR-152-3p) and pyruvate dehydrogenase kinase 4 (PDK4) in sepsis patients and LPS-treated HPAEpiC were detected by quantitative real-time PCR and western blot. Cell viability and apoptosis were assessed by Counting Kit-8 (CCK-8) assay and flow cytometry. The concentrations of inflammatory factors were tested by Enzyme-linked immunosorbent assay. Oxidative stress was evaluated by the levels of reactive oxygen species and superoxide dismutase using corresponding commercial kits. The targeting relationship between miR-152-3p and CASC2 or PDK4 was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.

Results

CASC2 and PDK4 were down-regulated, while miR-152-3p was up-regulated in sepsis patients and LPS-stimulated HPAEpiC. Overexpression of CASC2 relieved the LPS-resulted cell viability inhibition, apoptosis promotion, inflammatory and oxidative damages in HPAEpiC. In addition, miR-152-3p was a miRNA target of CASC2 and CASC2 alleviated cell injury in LPS-disposed HPAEpiC by sponging miR-152-3p. Moreover, miR-152-3p directly targeted PDK4 and CASC2 increased the PDK4 expression by depending on the sponge effect on miR-152-3p. Meanwhile, inhibition of miR-152-3p attenuated LPS-triggered HPAEpiC injury by upregulating the level of PDK4.

Conclusion

These results suggested that CASC2 ameliorated the LPS-induced injury in HPAEpiC via regulating miR-152-3p/PDK4 pathway.

KEYWORDS:

• Acute lung injury
• CASC2
• miR-152-3p
• PDK4
• sepsis

Ethics approval and consent to participate

This study was permitted by the Ethics Committee of Shanxi Provincial People’s Hospital and was carried out according to the guidelines of Declaration of Helsinki. All participants signed the written informed consent.

Competing interests

The authors declare that they have no competing interests.

Author contributions

Dongwu Shi designed and supervised the study. Lili Zhu conducted the experiments and drafted the manuscript. Jianghong Cao collected and analyzed the data. Lu Song contributed the methodology and edited the manuscript. All authors read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.