Suppression of miR-127 protects PC-12 cells from LPS-induced inflammatory injury by downregulation of PDCD4

• Published in: Biomedicine & pharmacotherapy Vol. 96; pp. 1154 - 1162
• Main Authors: Zhang, Zaiqing, Wan, Faqing, Zhuang, Qingshan, Zhang, Yinghua, Xu, Zhaowan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2017
• Subjects: Inflammation; LPS; miR-127; PC-12 Cells; PDCD4; SCI; TLR4; miR-127; SCI; PDCD4; Inflammation; TLR4; LPS; PC-12 Cells
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.11.107

Spinal cord injury (SCI) is one of the most debilitating injuries. Inflammatory response plays a central role in regulating the pathogenesis of acute and chronic SCI. Our study explores the role of miR-127 in inflammatory injury induced by LPS. PC-12 cells were treated with LPS to induce inflammatory injury. The expression of miR-127 and PDCD4 was altered by transient transfection. Cell viability was measured using CCK-8 assay and apoptosis using flow cytometry. The expression of miR-127 was measured by qRT-PCR. The concentrations of TNF-α and IL-6 were detected by ELISA. The levels of TLR4, PDCD4, BCL6, core factors of JNK and NF-κB pathway were assessed by RT-PCR/western blot. Dual luciferase reporter assay was conducted to verify the relationship between miR-127 and BCL6. LPS induced inflammatory injury in PC-12 cells. LPS also increased the expression of miR-127 and PDCD4. miR-127 overexpression promoted the LPS-induced inflammatory injury while miR-127 suppression inhibited the injury. BCL6 was a target of miR-127 in PC-12 cells. In addition, miR-127 positively regulated PDCD4 expression, and PDCD4 showed a similar effect on LPS-induced injury in PC-12 cells. We also found that miR-127 and PDCD4 enhanced the activation of JNK and NF-κB pathway. Further, the expressions of miR-127 and PDCD4 were both upregulated in ASCI rats. Our present study demonstrated that miR-127 inhibition might exert a protective role in LPS-injured PC-12 cells through regulation of PDCD4 expression and the further downstream signaling pathway.