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Transcriptional inhibition of miR-486-3p by BCL6 upregulates Snail and induces epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis.

Authors :
Yan, Ziyan
Ao, Xingkun
Liang, Xinxin
Chen, Zhongmin
Liu, Yuhao
Wang, Ping
Wang, Duo
Liu, Zheng
Liu, Xiaochang
Zhu, Jiaojiao
Zhou, Shenghui
Zhou, Pingkun
Gu, Yongqing
Source :
Respiratory Research; 4/28/2022, Vol. 23 Issue 1, p1-17, 17p
Publication Year :
2022

Abstract

<bold>Background: </bold>Ionizing radiation (IR) can induce pulmonary fibrosis by causing epithelial mesenchymal transition (EMT), but the exact mechanism has not been elucidated. To investigate the molecular mechanism of how radiation induces pulmonary fibrosis by altering miR-486-3p content and thus inducing EMT.<bold>Methods: </bold>The changes of miR-486-3p in cells after irradiation were detected by RT-qPCR. Western blot was used to detect the changes of cellular epithelial marker protein E-cadherin, mesenchymal marker N-cadherin, Vimentin and other proteins. The target gene of miR-486-3p was predicted by bioinformatics method and the binding site was verified by dual luciferase reporter system. In vivo experiments, adeno-associated virus (AAV) was used to carry miR-486-3p mimic to lung. Radiation-induced pulmonary fibrosis (RIPF) model was constructed by 25Gy60Co γ-rays. The structural changes of mouse lung were observed by HE and Masson staining. The expression of relevant proteins in mice was detected by immunohistochemistry.<bold>Results: </bold>IR could decrease the miR-486-3p levels in vitro and in vivo, and that effect was closely correlated to the occurrence of RIPF. The expression of Snail, which induces EMT, was shown to be restrained by miR-486-3p. Therefore, knockdown of Snail blocked the EMT process induced by radiation or knockdown of miR-486-3p. In addition, the molecular mechanism underlying the IR-induced miRNA level reduction was explored. The increased in BCL6 could inhibit the formation of pri-miR-486-3p, thereby reducing the levels of miR-486-3p in the alveolar epithelial cells, which would otherwise promote EMT and contribute to RIPF by targeting Snail.<bold>Conclusion: </bold>IR can exacerbate RIPF in mice by activating the transcription factor BCL6, which inhibits the transcription of miR-486-3p and decreases its content, which in turn increases the content of the target gene slug and triggers EMT. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14659921
Volume :
23
Issue :
1
Database :
Complementary Index
Journal :
Respiratory Research
Publication Type :
Academic Journal
Accession number :
156579176
Full Text :
https://doi.org/10.1186/s12931-022-02024-7