SNHG3 silencing suppresses the malignant development of triple-negative breast cancer cells by regulating miRNA-326/integrin α5 axis and inactivating Vav2/Rac1 signaling pathway

P. Wang, G.-Z. Liu, J.-F. Wang, Y.-Y. Du

Department 1 of Breast Surgery, Department 2 of Breast Surgery; Linyi Cancer Hospital, Linyi, Shandong, China. btklct@163.com

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• Oncology

OBJECTIVE: Long non-coding RNA small nucleolar RNA host gene 3 (SNHG3) has been shown to participate in several tumorigenesis. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is the first leading cause of new cancer diagnoses in women globally. However, the role of SNHG3 remains little known in breast cancers, especially in TNBC.

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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