LncRNA SNHG14 Plays a Role in Sepsis-Induced Acute Kidney Injury by Regulating miR-93.

Chuanchuan Shi,Qi Li,Yuqian Zhao,Jianguo Li,Agnieszka Dobrzyn

doi:10.1155/2021/5318369

Abstract

Acute kidney injury (AKI) is a common organ injury in sepsis, which leads to poor prognosis. Long noncoding RNA (lncRNA) small nucleolus RNA host gene 14 (SNHG14) was recognized to induce cell injury in LPS-induced acute lung injury and Parkinson's disease. We want to investigate the functions and mechanisms of SNHG14 in sepsis-induced AKI. Increased expression of SNHG14 was observed in LPS-induced HK-2 cells, and this was due to the activation of the TLR4/NF-κB pathway. In vitro studies showed that SNHG14 was involved in the oxidative stress, inflammation, and apoptosis of LPS-induced HK-2 cells. Further investigations confirmed that SNHG14 exerted the functions via miR-93 which could regulate the activation of NF-κB and STAT3 signaling by targeting IRAK4 and IL-6R. We also found that silencing SNHG14 also alleviated cellular injury processes of IL-1β and IL-6 in HK-2 cells via miR-93. We demonstrate that SNHG14 accelerates cellular injury in sepsis-induced AKI by activating IRAK4/NF-κB and IL-6R/STAT3 signaling via miR-93.

Highlights

Sepsis is a deadly inflammatory disease caused by infection which is characterized by the systemic inflammatory response syndrome (SIRS), leading to failure of multiple organs [1, 2]
To investigate the inducement of small nucleolus RNA host gene 14 (SNHG14) upregulation, we found that NFκB was a potential transcription factor that might bind to a SNHG14 promoter using the TRANSFAC database (Figure 1(b)) and the TLR4/NF-κB pathway was significantly activated in LPS-induced HK-2 cells as expected (Figure 1(c))
Knockdown of SNHG14 reduced the expression of IL-6R and IRAK4 and blocked the activation of downstream NF-κB and STAT3 signaling in LPS-induced HK-2 cells (Figure 4(f)). All of these results proved that SNHG14/miR-93 activates NF-κB and STAT3 signaling through mediating IRAK4 and IL-6R

Summary

Introduction

Sepsis is a deadly inflammatory disease caused by infection which is characterized by the systemic inflammatory response syndrome (SIRS), leading to failure of multiple organs [1, 2]. LPS-induced HK-2 cell is a mature cell model for sepsis-induced AKI in vitro which has been widely used for studying mechanisms of this disease [11,12,13]. Noncoding RNAs are new players found in disease progression of sepsis-induced AKI [14]. Many long noncoding RNAs (lncRNAs) had been verified to play critical roles in sepsis-induced AKI [15,16,17]. LncRNA small nucleolus RNA host gene 14 (SNHG14) had been confirmed by a large number of studies to play the role of oncogenesis in multiple tumors to promote malignant progression [18,19,20]. Its biological roles in sepsis-induced AKI still remains to be investigated

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Conclusion