Long noncoding RNA HOTAIR functions as ceRNA to regulate MMP2 in paraquat induced lung epithelial-mesenchymal transition

Paraquat (PQ) poisoning induces epithelial-mesenchymal transition (EMT) in the lungs, resulting in pulmonary fibrosis with a poor prognosis. Although competitive endogenous RNA (ceRNA) networks are known to exert post-transcriptional regulatory effects, the roles of such networks in PQ-induced EMT remain unknown. We explored the potential ceRNA network involved in PQ-induced pulmonary EMT. The male BALB/c mice were injected with 10 mg/kg PQ intraperitoneally and the lungs were harvested at 21st day. The A549 cells were treated with 60 mu mol/L PQ for 6 days. We determined the expression level of epithelia cadherin (E-cadherin) and a-smooth muscle actin (alpha-SMA) in the lungs and A549 cells after PQ exposure. We also detected the expression level of the long noncoding RNA (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR), microRNA-17-5p (miR-17-5p), and matrix metalloproteinase 2 (MMP2). We used specific siRNA to determine the influence of HOTAIR on MMP2. We also transfected a mimic or inhibitor of miR-17-5p to explore its role. Moreover, we used the luciferase reporter gene assay to confirm the relationship between miR-17-5p and HOTAIR or MMP2. In this study, we found that MMP2 and HOTAIR were upregulated and miR-17-5p was downregulated in PQ-induced EMT. The knockdown of HOTAIR decreased the expression of MMP2, and the upregulation of miR-17-5p suppressed HOTAIR and MMP2. Apparently, the downregulation of miR-17-5p increased the expression of HOTAIR and MMP2. The expression of alpha-SMA was negatively regulated by miR-17-5p after PQ exposure. In addition, the luciferase reporter gene assay confirmed that HOTAIR and MMP2 had direct binding sites with miR-17-5p. In conclusion, this study showed that the HOTAIR could act as a ceRNA for miR-17-5p to regulate MMP2 expression in PQ-induced pulmonary EMT.

Automated summary

The study revealed that in PQ-induced pulmonary EMT, HOTAIR acts as a ceRNA to regulate MMP2 expression by modulating miR-17-5p. MiR-17-5p negatively regulates HOTAIR and MMP2, while the downregulation of miR-17-5p increases the expression of HOTAIR and MMP2.