Bone Marrow Mesenchymal Stem Cell (BMSC)-Derived Exosomal miR-168-5p Inhibits Proliferation and Chemotherapy Resistance in Gastric Cancer by Downregulation of Cyclin D1 and P Glycoprotein

Abstract

miR-168-5p is indicated as an upstream effector of the tumor suppressor signal pathway in ovarian cancer and bladder cancer, but the role in gastric cancer (GC) remains unknown. This study aims to reveal the expression and significance of miR-168-5p in GC. RT-qPCR analysis was used to detect the expression of miR-168-5p in GC tissues and plasma, and the relationship of miR-168-5p and CCND1 was evaluated. GC cells were co-cultured with BMSCs or transfected with miR-168-5p mimic. CCK-8 assay and flow cytometry were conducted to assess the effect of miR-168-5p in GC and the interaction between BMSCs and cancer cell progression. Animal experiment was established to explore the in vivo effect of miR-168-5p. miR-168-5p is poorly expressed in gastric cancer cells and the plasma of patients with gastric cancer. BMSC co-culture is similar to miR-168-5p mimic induced miR-168-5p expression increase. miR-168-5p overexpression decreased the proliferative, invasive and migratory capacities of GC cells, and promoted apoptosis. Mechanically, miR-168-5p targeted and decreased the expression of CCND1. Additionally, the low miR-168-5p expression in GC was closely related to poor prognosis and malignant transformation. BMSC exosomes carrying miR-168-5p suppress cell progression in GC when inhibiting the expression of CCND1 and P glycoprotein, which indicates potential diagnostic and prognostic value of miR-168-5p and helps the development of miR-168-5p-based treatment for drug-resistant GC.