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

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.