Knockdown of lncRNA SNHG14 alleviates LPS-induced inflammation and apoptosis of PC12 cells by regulating miR-181b-5p

Abstract

Spinal cord injury (SCI) is a traumatic central nervous system disorder that leads to permanent functional loss, and unavailable treatment of this disease results in poor quality of life. However, the specific role of long non-coding RNA small nucleolar RNA host gene 14 (lncRNA SNHG14) in SCI has not been fully studied. The aim of the current study was to investigate the role of SNHG14 and its regulatory mechanism in lipopolysaccharide (LPS)-induced PC-12 cells. LPS was used to stimulate PC-12 cells to simulate inflammatory injury following SCI in vitro. Cell viability and apoptosis were respectively assessed by Cell Counting Kit-8 assay and TUNEL assay. Western blotting was performed to detect the expressions of apoptosis-related proteins. The mRNA levels of SNHG14 and microRNA (miR)-181b-5p were detected by reverse transcription-quantitative PCR. The target of SNGH14 was predicted by bioinformatics analysis and subsequently validated by a luciferase reporter assay. ELISA was then used to detect the levels of inflammatory factors. The results indicated that LPS induced inflammation, decreased cell viability and increased the apoptosis of PC-12 cells. Interference of SNHG14 alleviated this type of injury of PC-12 cells. Bioinformatics prediction and luciferase reporter assay demonstrated that miR-181b-5p could directly bind to SNHG14. Moreover, mechanistic investigations revealed that the miR-181b-5p inhibitor could reverse the inhibitory effects of SNHG14 silencing on cell viability, inflammation and apoptosis of PC-12 cells. To conclude, the present results showed that SNHG14 knockdown alleviated PC-12 cell inflammation and apoptosis induced by LPS via regulating miR-181b-5p, which might provide a novel insight into the treatment of SCI.

Identification Of A New Role Of miR-199a-5p As Factor Implied In Neuronal Damage: Decreasing The Expression Of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.

“…Our validation of a direct regulation of XIAP expression by miR-199a-5p may have a functional impact on the triggered processes of the secondary damage after SCI such as apoptotic cell death. Our bioinformatic studies identified a total of six miRNAs candidates as regulators of XIAP, of which the down-regulated miR-340-5p and some miR-181 family members have been related to the treatment of SCI [62][63][64]. On the other hand, the upregulation of miR-21a-5p may have a protective effect on neurons after SCI by the regulation of PDCD4/caspase-3 pathway [55].…”

Research Progress of Long Non-coding RNAs in Spinal Cord Injury

“…LncRNA Vof-16 upregulates the expression of pro-inflammatory cytokines TNF-α and IL-6 by targeting rno-miR-346/rno-miR-205/rno-miR-874-3p and mediates inflammatory response during spinal cord injury [ 50 ]. Similarly, LncRNA SNHG14 plays a similar role in inflammatory injury in PC12 cells by binding to miR-181b-5p [ 51 ].…”

Overexpression of LncRNA SNHG14 as a biomarker of clinicopathological and prognosis value in human cancers: A meta-analysis and bioinformatics analysis

“…It is a proven proto-oncogene in various cancers, including lung and cervical cancer. It is essential in activating inflammatory microglia, sepsis-induced acute kidney injury, and LPS-induced acute kidney injury ( Zhong et al, 2019 ; Jiang et al, 2021 ; Shi et al, 2021 ; Yang et al, 2021 ). Xie et al (2020) identified that SNHG14 regulates E-cadherin expression by interacting with EZH2, enhancing the progression of pancreatic ductal adenocarcinoma.…”