Affiliations: [a] The Second Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China | [b] Department of Anesthesiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China | [c] Department of Pathology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China | [d] Department of Medical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
Correspondence:
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Corresponding author: Shiping Zhang, Department of Anesthesiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, China. E-mail: [email protected].
Note: [1] Contributed equally.
Abstract: BACKGROUND: Low-density lipoprotein receptor-related protein 4 (LRP4) has been reported to be implicated in multiple types of cancers. However, the significance of LRP4 in gastric cancer (GC) remains poorly elucidated. Therefore, it’s urgent to investigate the importance and underlying mechanisms of LRP4 in GC. OBJECTIVE: To investigate the clinical roles of LRP4 in GC. METHODS: The LRP4 mRNA and miR-140-5p was measured by qRT-PCR. The protein expression was determined Western blot. Kaplan-Meier survival curves and Cox proportional hazard regression models were performed to evaluate prognosis. RESULTS: We demonstrated that LRP4 mRNA and protein was up-regulated in GC tissues for the first time. Its high expression was significantly correlated with malignant clinical features including TNM stage and lymph-node metastasis and poor prognosis for GC patients. LRP4 promotes migration, invasion and epithelial-mesenchymal transition (EMT) progress of GC cells. Mechanically, LRP4 regulated PI3K/AKT in GC cells. AKT inhibitors reversed the effects of LRP4. Finally, LRP4 was regulated by miR-140-5p in GC. CONCLUSIONS: Our findings showed that LRP4 has an important function in GC progression and promotes GC migration, invasion and EMT by regulating PI3K/AKT under regulation of miR-140-5p, providing a potential therapeutic target for GC.
