Role of miR-138 on Radio Sensitivity of Gastric Carcinoma Cells and Its Molecular Mechanism

Abstract

To explore FOXP4 and miR-138 in gastric carcinoma (GC) and its related mechanisms. Sixty-eight GC patients from January 2018 to January 2019 were selected as group A, and 66 healthy people as group B. GC cells and gastric mucosal epithelial cells were purchased, sh-FOXP4, si-FOXP4, NC, miR-138-inhibitor, and miR-138-mimics were transfected into MKN-45 and NCI-N87 cells. The FOXP4 and miR-138 expression levels in samples were tested by qRT-PCR, and N-cadherin, vimentin, Fibronectin, Slug, E-Cadherin and γ-catenin downstream proteins in cells were detected by WB. The proliferation was tested by MTT assay, invasion was tested by Transwell assay, and apoptosis was detected by flow cytometry assay. FOXP4 was highly expressed in GC, miR-138 was poorly expressed in GC, and AUC of FOXP4 and miR-138 was > 0.8. FOXP4 and miR-138 were tied to the age, gender, tumor invasion, differentiation degree, tumor location and TNM stage of GC patients. Silent expression of FOXP4 and overexpression of miR-138 can promote apoptosis, inhibit cell growth and epithelial-mesenchymal transition (ETM). The two also can inhibit N-cadherin, vimentin, Fibronectin and Slug proteins, and promote E-Cadherin and γ-catenin. Dual luciferase report confirmed that FOXP4 and miR-138 had targeted relationship. In terms of radiological parameters, the SF₂ and D₀ (Gy) values of transfected miR-138mimic+pcDNA3. 1-FOXP4 were dramatically higher than those of transfected miR-138mimic+pcDNA3. 1 cells, and SER was lower than those of transfected miR-138 mimic+ pcDNA3. 1 cells (P<0.05), suggesting FOXP4 partially adjusted the radiosensitization role of miR-138. In conclusion, miR-138 can regulate EMT of GC cells by adjusting FOXP4 and enhance radiosensitivity of those cells.