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Urothelial carcinoma-associated 1 enhances tamoxifen resistance in breast cancer cells through competitively inhibiting miR-18a / 北京大学学报(医学版)
Journal of Peking University(Health Sciences) ; (6): 295-302, 2017.
Artículo en Chino | WPRIM | ID: wpr-512640
ABSTRACT

Objective:

To investigate how urothelial carcinoma-associated 1 (UCA1) and miR-18a modulates acquired tamoxifen resistance and the relevant mechanisms in estrogen receptor (ER) positive cancer cells.

Methods:

qRT-PCR was performed to detect UCA1 and miR-18a expression in breast cancer cells.Dual luciferase assay was performed to detect the binding between miR-18a and UCA1 3′UTR.Tamoxifen sensitive MCF-7 cells were transfected with UCA1 expression vector or miR-18a inhi-bitors.Tamoxifen resistant LCC9 and BT474 cells were transfected with UCA1 siRNA or miR-18a mi-mics.CCK-8 assay was performed to detect cell viability.Soft agar assay was performed to assess cell colony formation.Flow cytometric analysis was performed to check cell cycle distribution.

Results:

UCA1 was significantly upregulated in tamoxifen resistant LCC2,LCC9,and BT474 cells than in tamoxifen sensitive MCF-7 cells.UCA1 expression was significantly upregulated in MCF-7 cells after treatment with 0.1 μmol/L tamoxifen.UCA1 overexpression enhanced cell viability of MCF-7 cells after tamoxifen treatment,while UCA1 siRNA significantly suppressed viability of LCC9 and BT474 cells after tamoxifen treatment.In MCF-7 cells,compared with vector control+tamoxifen group,the average cell colony number and colony size of the UCA1+tamoxifen group was 19.0% more and 29.0% larger respectively,while the proportions of the cells in G1 phase and in S phase were 7.3% lower and 6.7% higher respectively.In BT474 cells,compared with siRNA control+tamoxifen group,the average cell colony number and colony size of the si-UCA1+tamoxifen group were 54.0% less and 42.0% smaller respectively,while the proportions of the cells in G1 phase and in S phase were 9.0% higher and 6.2% lower respectively.UCA1 directly interacted with miR-18a and reduced its expression in ER positive breast cancer cells.Knockdown of miR-18a increased viability of MCF-7 cells after tamoxifen treatment,while miR-18a overexpression significantly reduced viability of BT474 cells after tamoxifen treatment.In MCF-7 cells,compared with miRNA inhibitor control+tamoxifen group,the average cell colony number and colony size of the miR-18a inhibitor+tamoxifen group were 15.0% more and 33.0% larger respectively,while the proportions of the cells in G1 phase and in S phase were 8.8% lower and 5.3% higher respectively.In BT474 cells,compared with miRNA control+tamoxifen group,the average cell colony number and colony size of the miR-18a mimics+tamoxifen group were 47.0% less and 25.0% smaller respectively,while the proportions of the cells in G1 phase and in S phase were 13.3% higher and 7.9% lower respectively.

Conclusion:

UCA1 can increase tamoxifen resistance of ER positive breast cancer cells via competitively inhibiting of miR-18a.

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Idioma: Chino Revista: Journal of Peking University(Health Sciences) Año: 2017 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Idioma: Chino Revista: Journal of Peking University(Health Sciences) Año: 2017 Tipo del documento: Artículo