Abstract | OBJECTIVE: MATERIALS AND METHODS: Expression of SNHG3, miRNA-326-5p (miR-326) and integrin α5 (ITGA5) was detected using Real Time-PCR and Western blotting. Cell viability, apoptosis, migration, and invasion were measured by methyl thiazolyl tetrazolium assay, flow cytometry, and transwell assays, respectively. Vav2/Rac1 signaling pathway was evaluated by Western blotting by analyzing Vav2 and Rac1 levels. The interaction among miR-326, SNHG3 and ITGA5 was confirmed by Dual- Luciferase reporter assay. RESULTS: We found that the expression of SNHG3 and ITGA5 was upregulated and miR-326 was downregulated in TNBC tumors and cell lines (MDA-MB-231, BT-549, MDA-MB-468 and SUM159). Functionally, both SNHG3 silencing and miR-326 overexpression enhanced cell apoptosis, but depressed cell viability, migration and invasion in MDA-MB-231 and BT-549 cells, as well as inhibited Vav2 and Rac1 expression. Notably, miR-326 deletion could abolish the tumor-suppressive role of SNHG3 silencing; meanwhile, the similar anti- tumor effect of miR-326 overexpression was abrogated by ITGA5 restoration. Mechanically, SNHG3 silencing downregulated ITGA5 expression by functioning as a molecular "sponge" for miR-326. CONCLUSIONS: Silencing of SNHG3 suppressed the malignant development of TNBC cells, at least partially, through miR-326/ITGA5 axis and inhibiting Vav2/Rac1 signaling pathway.
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Authors | P Wang, G-Z Liu, J-F Wang, Y-Y Du |
Journal | European review for medical and pharmacological sciences
(Eur Rev Med Pharmacol Sci)
Vol. 24
Issue 10
Pg. 5481-5492
(05 2020)
ISSN: 2284-0729 [Electronic] Italy |
PMID | 32495883
(Publication Type: Journal Article)
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Chemical References |
- ITGA5 protein, human
- Integrins
- MicroRNAs
- Proto-Oncogene Proteins c-vav
- RAC1 protein, human
- RNA, Long Noncoding
- VAV2 protein, human
- rac1 GTP-Binding Protein
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Topics |
- Cells, Cultured
- Gene Silencing
- Humans
- Integrins
(genetics, metabolism)
- MicroRNAs
(genetics, metabolism)
- Proto-Oncogene Proteins c-vav
(genetics, metabolism)
- RNA, Long Noncoding
(genetics, metabolism)
- Signal Transduction
- Triple Negative Breast Neoplasms
(metabolism, pathology)
- rac1 GTP-Binding Protein
(genetics, metabolism)
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