Background Hypoxia is an important process that involved in the tumor microenvironment. In addition, hypoxic tumor cell-derived exosomes could promote tumor growth and angiogenesis. Thus, we aimed to investigate whether exosomes could regulate tumor development and progression under hypoxia in breast cancer. Methods The level of SNHG1 in hypoxic breast cancer cells and exosomes derived from hypoxic breast cancer cells was determined by real-time qPCR assay. Bioinformatics prediction and dual-luciferase reporter assays were used to determine the interaction between SNHG1, miR-216b-5p and JAK2. Results We found that comparing with exosomes derived from normoxia breast cancer cells, exosomes derived from hypoxic breast cancer cells could promote the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). In addition, SNHG1 level was significantly upregulated in exosomes derived from hypoxic breast cancer cells. Moreover, exosome-mediated delivery of SNHG1 siRNA3 markedly reversed the effects of exosome-mediated delivery of SNHG1 on HUVECs. Mechanically, SNHG1 could increase the level of JAK2 by competitively binding to miR-216b-5p. Additionally, exosome-mediated delivery of SNHG1 was found to promote breast cancer growth in vivo. Conclusion Collectively, our study revealed that exosomal SNHG1 from hypoxic breast cancer cells could promote tumor angiogenesis and growth via regulating miR-216b-5p/JAK2 axis, suggesting that SNHG1 may serve as a potential therapeutic target for breast cancer.

Background Breast cancer (BC) has posed a great threat to world health as the leading cause of cancer death among women. Previous evidence demonstrated that germ cell-specific gene 2 (GSG2) was involved in the regulation of multiple cancers. Thus, the clinical value, biological function and underlying mechanism of GSG2 in BC were investigated in this study. Methods The expression of GSG2 in BC was revealed by immunohistochemistry (IHC), qPCR and western blotting. Secondly, the biological function of GSG2 in BC was evaluated by MTT assay, flow cytometry, Transwell assay and wound healing assay. Furthermore, the potential molecular mechanism of GSG2 regulating the progression of BC by co-immunoprecipitation (Co-IP) and protein stability detection. Results Our data indicated that GSG2 was frequently overexpressed in BC. Moreover, there was a significant correlation between the GSG2 expression and the poor prognosis of BC patients. Functionally, GSG2 knockdown inhibited the malignant progression of BC characterized by reduced proliferation, enhanced apoptosis and attenuated tumor growth. Migration inhibition of GSG2 knockdown BC cells via epithelial-mesenchymal transition (EMT), such as downregulation of Vimentin and Snail. In addition, E2F transcription factor 1 (E2F1) was regarded as a target protein of GSG2. Downregulation of E2F1 attenuated the promoting role of GSG2 on BC cells. Mechanistically, knockdown of GSG2 accelerated the ubiquitination of E2F1 protein, which was mediated by E3 ubiquitin ligase MDM2. Conclusions GSG2 facilitated the development and progression of BC through MDM2-mediated ubiquitination of E2F1, which may be a promising candidate target with potential therapeutic value.