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Loss of MEG3 and upregulation of miR-145 play an important role in the invasion and migration of Cr(VI)-transformed cells
- Source :
- Heliyon, Vol 8, Iss 8, Pp e10086- (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 24058440
- Volume :
- 8
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Heliyon
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9f0f6ace0c540feb38576c8355bb3cf
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.heliyon.2022.e10086