Sepsis refers to a severe clinical condition caused by the body’s excessive responses to bacterial, viral, and fungal infections [
1]. Other than ICU treatment, there are no effective approaches for severe septic shock [
2]. As a consequence, sepsis is correlated with an unacceptably high mortality rate [
3]. It is estimated that 1 out 3 deaths in hospitals are at least partially caused by sepsis [
4]. Sepsis-caused inflammation and cell injuries bring damages to almost all organs, such as the lung [
5,
6]. Acute lung injury or respiratory failure is a devastating complication of sepsis, resulting in death or disabilities even after active treatments [
6]. Therefore, the prevention and treatment of lung injury are critical for the recovery of sepsis patients.
Sepsis is essentially a type of inflammatory disease, requiring the involvement of multiple players [
7,
8]. With the increased elucidation of the molecular mechanisms of sepsis, some molecular factors, such as ALK, have been proven to be potential targets for developing novel therapies against sepsis and sepsis-induced organ failures, such as targeted therapy to treat sepsis by regulating regulated gene expression [
9,
10]. However, to date, effective targets for sepsis targeted therapy remain lacking. Circular RNAs, or circRNAs, are covalently closed single-strand RNA transcripts that participate in human diseases, including sepsis, possibly by regulating gene expression [
11,
12], suggesting that they are potential targets for sepsis-targeted therapy. However, the functions of most circRNAs in sepsis have not been elucidated. CircRNA circFADS2 is proven to play a protective role in LPS-induced cell apoptosis, contributing to sepsis [
13]. Our preliminary RNA-seq analysis revealed that the altered circFADS2 expression in sepsis is inversely correlated with miR-15a-5p, which may promote pulmonary diseases [
14]. Therefore, this study was performed to explore the role of circFADS2 in sepsis and its interaction with miR-15a-5p, with a focus on sepsis-induced lung injury.