Targeting a novel LncRNA SNHG15/miR-451/c-Myc signaling cascade is effective to hamper the pathogenesis of breast cancer (BC) in vitro and in vivo

Abstract

Abstract Background To our knowledge, LncRNA SNHG15 exerted its tumor-promoting effects to facilitate the development of breast cancer (BC), but there still needed more data to elucidate the potential underlying mechanisms. Methods We examined genes expression status by performing Real-Time qPCR and Western Blot analysis, and cellular functions, including cell proliferation, viability, apoptosis, mobility, were measured by using the CCK-8 assay, colony formation assay, trypan blue staining assay, flow cytometer (FCM), transwell assay and wound scratch assay, respectively. The predicted targeting sites in LncRNA SNHG15, miR-451 and c-Myc 3′UTR were validated by dual-luciferase reporter gene system assay. Finally, we established the tumor-bearing mice models, and the expression status, including its enrichment and cellular localization were examined by immunohistochemistry (IHC) assay. Results Our data indicated LncRNA SNHG15 upregulated c-Myc to facilitate BC progression by sponging miR-451 in a competing endogenous RNA (ceRNA)-dependent manner in vitro and in vivo. Specifically, LncRNA SNHG15 and c-Myc were upregulated, while miR-451 was downregulated in BC cells and clinical tissues, compared to their normal counterparts. In addition, miR-451 negatively correlated with LncRNA SNHG15 and c-Myc, and LncRNA SNHG15 was positively relevant to c-Myc in BC tissues. Next, we validated that LncRNA SNHG15 sponged miR-451 to upregulate c-Myc in BC cells. Further gain- and loss-of-function experiments evidenced that LncRNA SNHG15 promoted, while miR-451 inhibited malignant phenotypes, including cell proliferation, viability, migration, invasion and epithelial-mesenchymal transition (EMT) in BC cells. Interestingly, the inhibiting effects of LncRNA SNHG15 ablation on BC progression were abrogated by both silencing miR-451 and overexpressing c-Myc. Conclusions We concluded that targeting the LncRNA SNHG15/miR-451/c-Myc signaling cascade was novel to hamper BC progression, which broadened our knowledge in this field, and provided potential biomarkers for BC diagnosis and treatment.