» Articles » PMID: 26379838

Silencing of DUSP6 Gene by RNAi-mediation Inhibits Proliferation and Growth in MDA-MB-231 Breast Cancer Cells: an in Vitro Study

Overview
Specialty General Medicine
Date 2015 Sep 18
PMID 26379838
Citations 11
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells.

Methods: DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T-test (two-tailed) was used to compare differences between groups, and the significance level was set at P<0.05.

Results: DUSP6 mRNA expression and protein expression were reduced after transfection with DUSP6-siRNA directly and similar trend with transfection with miR-145. The treated group with DUSP6-siRNA or miR-145 suppressed MDA-MB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase.

Conclusions: DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells.

Citing Articles

A distinct transcriptome characterizes neural crest-derived cells at the migratory wavefront during enteric nervous system development.

Stavely R, Hotta R, Guyer R, Picard N, Rahman A, Omer M Development. 2023; 150(5).

PMID: 36779913 PMC: 10108706. DOI: 10.1242/dev.201090.


Dual-specificity phosphatase (DUSP6) in human glioblastoma: epithelial-to-mesenchymal transition (EMT) involvement.

Zuchegna C, Di Zazzo E, Moncharmont B, Messina S BMC Res Notes. 2020; 13(1):374.

PMID: 32771050 PMC: 7414695. DOI: 10.1186/s13104-020-05214-y.


DUSP6 protects murine podocytes from high glucose‑induced inflammation and apoptosis.

Chen L, Wang Y, Luan H, Ma G, Zhang H, Chen G Mol Med Rep. 2020; 22(3):2273-2282.

PMID: 32705203 PMC: 7411363. DOI: 10.3892/mmr.2020.11317.


Overexpression of DUSP6 enhances chemotherapy-resistance of ovarian epithelial cancer by regulating the ERK signaling pathway.

Gao Y, Li H, Han Q, Li Y, Wang T, Huang C J Cancer. 2020; 11(11):3151-3164.

PMID: 32231719 PMC: 7097933. DOI: 10.7150/jca.37267.


Down-regulation of CCL17 in cancer-associated fibroblasts inhibits cell migration and invasion of breast cancer through ERK1/2 pathway.

Li J, Yang C, Yang J, Zou L Cancer Manag Res. 2019; 11:7439-7453.

PMID: 31496803 PMC: 6689663. DOI: 10.2147/CMAR.S211651.


References
1.
Carthew R, Sontheimer E . Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009; 136(4):642-55. PMC: 2675692. DOI: 10.1016/j.cell.2009.01.035. View

2.
Chan D, Liu V, Tsao G, Yao K, Furukawa T, Chan K . Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells. Carcinogenesis. 2008; 29(9):1742-50. DOI: 10.1093/carcin/bgn167. View

3.
Manzano R, Martinez-Navarro E, Forteza J, Brugarolas A . Microarray phosphatome profiling of breast cancer patients unveils a complex phosphatase regulatory role of the MAPK and PI3K pathways in estrogen receptor-negative breast cancers. Int J Oncol. 2014; 45(6):2250-66. PMC: 4215587. DOI: 10.3892/ijo.2014.2648. View

4.
Li X, Luo Q, Wei C, Li D, Fang L . siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells. Int J Clin Exp Pathol. 2014; 7(1):92-100. PMC: 3885463. View

5.
Bermudez O, Pages G, Gimond C . The dual-specificity MAP kinase phosphatases: critical roles in development and cancer. Am J Physiol Cell Physiol. 2010; 299(2):C189-202. DOI: 10.1152/ajpcell.00347.2009. View