The Effects And Mechanism Of LncRNA SNHG3 On Bone Mestastasis Microenvironment Of Breast Cancer

Objective: This study intends to explore the effect and mechanism of lncRNA SNHG3 in breast cancer cells on osteogenic differentiation ability of BMSCs and its mechanism in tumor microenvironment.Methods: The expression level of lncRNA SNHG3 in breast cancer tissues was analyzed by TCGA database.Lnc RNA SHNG3 level of clinical tissues and breast cancer cell lines was determined by quantitative real-time polymerase chain reaction(q RT-PCR).A stable MDA-MB-231 cell line with lncRNA SNHG3 knockdown was constructed and verified by real-time quantitative PCR.ALP staining,ALP activity identification and western blot of OPG,OSX,RUNX2,BMP2 together with BMP3 were carried out to verify the osteogenesis of bone marrow mesenchymal stem cells(BMSCs)both in vitro and in vivo.Exosomes secreted from the control group and MDA-MB-231/sh SNHG3 group were characterized and sequenced,followed by q RT-PCR of miRNA validation to analyze the targeting miRNA of lncRNA SNHG3.Bioinformatics prediction and dual luciferase reporter gene assay were utilized to observe the binding sites of miR-1273g-3p on lncRNA SNHG3 and BMP3.Results: Lnc RNA SNHG3 was highly expressed in breast cancer tissues,and its expression level was positively correlated with breast cancer bone metastasis.The result of ALP staining,ALP activity detection and Western blot suggested the knock-down of lncRNA SNHG3 in breast cancer cells can significantly improve the osteogenic ability of BMSCs.Exosomes were detected in the extracted cell supernatant.In the interaction between breast cancer cells and BMSCs,the expression of bone morphogenetic protein 3(BMP3)was positively regulated by lncRNA SNHG3 / miR-1273g-3p / BMP3 axis in the intercellular communication between breast cancer cells and BMSCs.Conclusion: Knockdown of lncRNA SNHG3 in breast cancer cells promotes osteogenic differentiation of BMSCs in breast cancer bone microenvironment through lncRNA SNHG3 / miR-1273 g-3 p / BMP3 axis.The above results suggest that lncRNA SNHG3 may be a potential therapeutic target for bone metastasis of breast cancer.