LncRNA-RP11 Modulates TGF-β1-Activated Radiation-Induced Lung Injury Through Downregulating microRNA-29a.
Xi YangJianjiao NiYida LiLiqing ZouTiantian GuoYuan LiLi ChuZhengfei ZhuPublished in: Dose-response : a publication of International Hormesis Society (2020)
Radiation-induced lung injury (RILI) is one of the most serious complications of thoracic radiation and TGF-β1 is a central regulator of RILI. However, the molecular mechanism underlying the fine tuning of TGF-β1 signaling in RILI has not been fully understood. In the current study, differentially expressed long non-coding RNAs (LncRNAs) among human lung fibroblasts cell lines HFL-1 and WI-38 treated with TGF-β1, were identified by microarray and validated by real time PCR. LncRNA-RP11 was found to be the most increased LncRNA and it mediated the promotion of fibrogenic activity in human lung fibroblasts after TGF-β1 treatment. Bioinformatic analysis revealed that TGF-β1 may be associated with the component and structure of extracellular matrix in lung fibroblasts cells, and LncRNA-RP11 was predicted and confirmed to be a competing endogenous RNA by directly binding to miR-29a. Functional experiments investigating the biological role of LncRNA-RP11/miR-29a axis in RILI, were then carried out in human fibroblasts. The results showed that radiation promoted the expression of LncRNA-RP11, but regressed the expression of miR-29a. Furthermore, radiation elevated the expression of various common collagenic proteins, which could be abolished by overexpression of miR-29a.
Keyphrases
- long non coding rna
- poor prognosis
- radiation induced
- extracellular matrix
- transforming growth factor
- long noncoding rna
- radiation therapy
- cell proliferation
- epithelial mesenchymal transition
- endothelial cells
- induced apoptosis
- oxidative stress
- transcription factor
- real time pcr
- risk factors
- air pollution
- spinal cord injury
- binding protein
- newly diagnosed
- pi k akt
- replacement therapy