Abstract
BackgroundBrain metastasis (BM) is a dreadful complication that significantly impacts the quality of life in breast cancer patients. A key process during brain metastasis is the migration of cancer cells across blood–brain barrier (BBB). However, the role of snoRNAs regulating BBB in BM is still unknown.MethodsHere SNORic and GEO databases were used to identify differentially expressed snoRNAs between brain metastatic and non-metastatic breast cancer (BC) tissues. The effects of SNORA71B on the capacities of proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and BBB invasion of BC cells were evaluated by CCK8, transwell, western blot, and BBB model, respectively.ResultsSNORA71B was highly expressed in high BM BC tissues and cells compared to low BM BC controls. Survival analysis revealed high expression of SNORA71B was significantly associated with poor PPS and OS in breast cancer patients. ROC curve showed that SNORA71B might act as biomarker for breast cancer. Moreover, SNORA71B significantly promoted proliferation, migration, and invasion of BC cells with different BM abilities. Importantly, SNORA71B promoted the EMT process of low BM BC cells. SNORA71B knockdown inhibited the high BM BC cells across BBB, while EMT activator dramatically abrogated this inhibited effect.ConclusionsIn conclusion, SNORA71B promotes BC cells across the BBB partly via inducing EMT.
Highlights
Breast cancer (BC) is the most common cancer in women patients and develops to brain metastases (BM), which further severely impairs patients’ quality of life
To screen snoRNAs related to breast cancer (BC) metastasis, we first loaded GSE100534 microarray data and found that the expression of SNORA71B was significantly different and higher in breast cancer brain metastases (BCBM) tissues compared with relative lower Brain metastasis (BM) BC tissues (Fig. 1a)
The Post-Progression Survival (PPS) and Overall Survival (OS) using Kaplan–Meier Plotter analysis results showed that low expression of SNORA71B was correlated with better Overall Survival (OS) and Post-Progression Survival (PPS) in breast cancer patients (Fig. 1c, d)
Summary
Breast cancer (BC) is the most common cancer in women patients and develops to brain metastases (BM), which further severely impairs patients’ quality of life. Women patients with breast carcinoma have higher incidence of brain metastases compared with men. Brain metastasis (BM) is a dreadful complication that significantly impacts the quality of life in breast cancer patients. A key process during brain metastasis is the migration of cancer cells across blood–brain barrier (BBB). Methods Here SNORic and GEO databases were used to identify differentially expressed snoRNAs between brain metastatic and non-metastatic breast cancer (BC) tissues. Survival analysis revealed high expression of SNORA71B was significantly associated with poor PPS and OS in breast cancer patients. SNORA71B knockdown inhibited the high BM BC cells across BBB, while EMT activator dramatically abrogated this inhibited effect. Conclusions In conclusion, SNORA71B promotes BC cells across the BBB partly via inducing EMT
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