High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

Abstract

Background High-mobility group box 1 (HMGB1) is an essential contributor towards initiation and progression of many kinds of cancers. Nevertheless, our understanding of the molecular etiology of HMGB1-modulated vasculogenesis, as well as invasion, of breast cancer is poor. This study explored HMGB1 expression in breast cancer and its role in the development and spread of malignancy. Material/Methods We enrolled 15 patients with breast cancer who received primary surgery at the Department of Thyroid and Breast Surgery in our hospital. HMGB1 was recorded and analyzed. Results Our investigation successfully proves that HMGB1 is upregulated in breast cancer tissues in comparison to the surrounding non-malignant tissues. HMGB1 enhanced vessel formation in breast cancer tissues by regulating hypoxia-inducible factor 1 (HIF-1α), which in turn upregulates the expression of VEGF. Furthermore, HMGB1-mediated upregulation of HIF-1α relies on its ability to stimulate the phosphatidylinositol 3-kinase (PI3K) pathway to reinforce AKT subunit phosphorylation. HMGB1 overexpression reinforces the vasculogenesis in malignancies not only in vivo but also in vitro . Additionally, shRNA knockdown of HMGB1 prohibited the vessel-forming and invasive capabilities, downregulated VEGF and HIF-1α, and suppressed AKT phosphorylation in breast cancer cells. Most importantly, PI3K/AKT axis suppression eliminated the effect of HMGB1-modulated vascularization and invasion in breast cancer cells. Conclusions Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.

Circular RNA CirCHIPK3 promotes cell proliferation and invasion of breast cancer by sponging miR‐193a/HMGB1/PI3K/AKT axis

“…31 In a previous study, HMGB1 has been proven to be a regulator of PI3K/AKT in BC progression. 29 In our study, we found si-CirCHIPK3 inhibited HMGB1 and PI3K/AKT signaling indicating CirCHIPK3 could inhibit BC progression through regulating HMGB1/PI3K/AKT axis.…”

“…28 A previous study has proved that HMGB1 expression is strongly enhanced in BC tissues in comparison with the corresponding surrounding nonmalignant tissues. 29 In addition, high HMGB1 expression has been reported to be connected to all the hallmarks of malignancy, such as unlimited replicative potential, ability to form vessels, avoiding apoptosis, tolerance towards growth-suppressors, invasion, inflammation, and metastasis. 25 In our study, we showed CIRCHIPK3 and HMGB1 were both potential target genes of miR-193a through bioinformatic analysis and luciferase activity assay.…”

Curcumol attenuates liver sinusoidal endothelial cell angiogenesis via regulating Glis‐PROX1‐HIF‐1α in liver fibrosis

“…The ubiquitin‐proteasome system practically kept steady‐state levels low. Until recently, studies of post‐translational modifications of HIF‐1α were expanded to hydroxylation, phosphorylation, methylation and acetylation . In hepatocellular carcinoma, the homeobox protein PROX1 is overexpressed in hepatocytes and is required for cell migration.…”

Identification of hub genes in papillary thyroid carcinoma: robust rank aggregation and weighted gene co-expression network analysis

“…Meanwhile, KEGG terms such as transcriptional misregulation in cancer, Rap1 signaling pathway and PI3K-Akt signaling pathway were obtianed. PI3K-Akt signaling pathway had been reported to play an important role in the development of thyroid cancer [46,47], breast cancer [48], colorectal cancer [49], non-small cell lung cancer [50] and gastric cancer [51] etc.…”