Inhibition of miR‑214 attenuates the migration and invasion of triple‑negative breast cancer cells

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer. MicroRNA (miR)-214 is closely associated with controlling the development of tumor cells; therefore, in the present study, the target gene and effects of miR-214 on TNBC cells were explored. Luciferase activity was examined by luciferase reporter assay. The viability, invasion and migration of MDA-MB-231 TNBC cells were measured using Cell Counting kit-8, Transwell and wound-healing assays, respectively. The expression levels of various factors were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that the expression levels of miR-214 were higher and the levels of α1-antitrypsin (α1-AT) were lower in TNBC tissues compared with in normal tissues. Subsequently, α1-AT was revealed to be a target of miR-214. Furthermore, inhibition of miR-214 decreased cell viability, invasion and migration, enhanced the expression of E-cadherin and tissue inhibitor of metalloproteinases-2, and reduced the expression of metastatic tumour antigen 1 and matrix metalloproteinase-2. Inhibition of miR-214 also significantly downregulated the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and markedly downregulated that of phosphoinositide 3-kinase (PI3K); however, the expression levels of total PI3K, Akt and mTOR remained stable in all groups. Taken together, these findings indicated that α1-AT may be a target of miR-214. Downregulation of miR-214 markedly suppressed the viability, migration and invasion of MDA-MB-231 cells, and inhibited the PI3K/Akt/mTOR pathway. These findings suggested that miR-214 targeting α1-AT may be a potential mechanism underlying TNBC development.

Silencing the COPB2 gene decreases the proliferation, migration and invasion of human triple‑negative breast cancer cells

“…These observations are consistent with the proposal that the AKT signaling pathway promotes EMT transition and the proliferation of cancer cells (32,33). The present results are also consistent with those of various previous studies (34)(35)(36). For example, AKT phosphorylation is downregulated after silencing COPB2 in gastric cancer cells (27).…”

MicroRNA-214 in Health and Disease

“…However, this study would have benefited from cell-specific miR-214 knockdown, as systemic silencing may cause unintended effects. Nonetheless, these findings agreed with reports of miR-214 promoting breast cancer cell invasion, partly through targeting p53 [71] or α1-antitrypsin (α1-AT) [57]. As previously described in melanoma, breast cancer cell metastasis was hindered by inhibiting miR-214 or upregulating miR-148b which targets ALCAM and ITGA5 adhesion molecules [38].…”

Mechanisms behind Retinal Ganglion Cell Loss in Diabetes and Therapeutic Approach

“…In diabetic retinopathy there is a downregulation of Akt activity affecting a large number of pathways related to diverse cellular processes; ultimately, the resulting imbalance promotes RGC apoptosis. In the literature there are reports stating that A1AT can downregulate the PI3K/Akt/mTOR pathway in breast cancer cells, where this pathway is increased [163,164]. However, there are other reports remarking the role of A1AT as an up-regulator of the PI3K/Akt pathway, reducing neutrophil elastase-induced migration of lung cancer cells, tumor tissue proliferation and inflammatory microenvironment [161,162].…”