| Autor: |
Zhuo Zhang, Jingxia Li, Bo Yan, Huailu Tu, Chao Huang, Max Costa |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Heliyon, Vol 8, Iss 8, Pp e10086- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2405-8440 |
| DOI: |
10.1016/j.heliyon.2022.e10086 |
| Popis: |
Chronic exposure of human bronchial epithelial BEAS-2B cells to hexavalent chromium (Cr(VI)) causes malignant cell transformation. These transformed cells exhibit increases in migration and invasion. Neuronal precursor of developmentally downregulated protein 9 (NEDD9) is upregulated in Cr(VI)-transformed cells compared to that of passage-matched normal BEAS-2B cells. Knockdown of NEDD9 by its shRNA reduced invasion and migration of Cr(VI)-transformed cells. Maternally expressed gene 3 (MEG3), a long noncoding RNA, was lost and microRNA 145 (miR-145) was upregulated in Cr(VI)-transformed cells. MEG3 was bound to miR-145 and this binding reduced its activity. Overexpression of MEG3 or inhibition of miR-145 decreased invasion and migration of Cr(VI)-transformed cells. Overexpression of MEG3 was able to decrease miR-145 level and NEDD9 protein level in Cr(VI)-transformed cells. Ectopic expression of MEG3 was also shown to reduce β-catenin activation. Inhibition of miR-145 in Cr(VI)-transformed cells decreased Slug, an important transcription factor that regulates epithelial-to-mesenchymal transition (EMT). Inhibition of miR-145 was found to increase MEG3 in Cr(VI)-transformed cells. Further studies showed that mutation of MEG3 at the binding site for miR-145 did not change NEDD9 and failed to decrease invasion and migration. The present study demonstrated that loss of MEG3 and upregulation of miR-145 elevated NEDD9, resulting in activation of β-catenin and further upregulation of EMT, leading to increased invasion and migration of Cr(VI)-transformed cells. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
