Up-regulation of SNHG15 facilitates cell proliferation, migration, invasion and suppresses cell apoptosis in breast cancer by regulating miR-411-5p/VASP axis

L.-B. Liu, Z.-J. Jiang, X.-L. Jiang, S. Wang

Department of Colorectal Surgery, Department of Thyroid Breast Surgery, Department of Radiation; Affiliated Nanhua Hospital, University of South China, Hengyang, China. congkuanfaluo2003@yeah.net

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• Oncology

OBJECTIVE: Breast cancer (BC) is an intractable cancer with a rising incidence. Small nucleolar RNA host gene 15 (SNHG15) is a novel biomarker of multiple cancers. However, the molecular mechanism of SNHG15 during oncogenesis of BC is still poorly understood.

MATERIALS AND METHODS: Expression of SNHG15, microRNA (miR)-411-5p and vasodilator stimulated phosphoprotein (VASP) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by colony formation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was determined by flow cytometry and caspase-3 activity assay. Cell migration and invasion were examined by transwell assay. The interaction between miR-411-5p and SNHG15 or VASP was validated by dual-luciferase reporter assay. Protein expression of VASP, B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP-9, MMP-14) was measured by Western blot. Xenograft mice were established by subcutaneously injecting SKBR-3 cells transfected with sh-SNHG15 and sh-NC.

RESULTS: SNHG15 and VASP were over-expressed whereas miR-411-5p was low-expressed in BC tumors and cells compared with the normal counterparts. Next, SNHG15 knockdown attenuated cell proliferation, migration, invasion and stimulated cell apoptosis in BC. In addition, SNHG15 acted as a sponge while VASP acted as a target of miR-411-5p. Rescue experiment revealed that miR-411-5p inhibitor could alleviate SNHG15 silencing-induced inhibitive effects on cell proliferation, migration, invasion and promotive effects on cell apoptosis. Similarly, VASP attenuated the regulatory effects of SNHG15 silencing on BC cell progression. Furthermore, SNHG15 elimination hindered tumor growth in vivo.

CONCLUSIONS: SNHG15 contributes to BC cell progression by sponging miR-411-5p and enhancing VASP expression, providing essential biomarkers for BC therapy.

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