Gastric cancer (GC) is a common malignant tumor worldwide, with a high incidence and low survival rate. The transforming growth factor-beta (TGFβ) signaling pathway usually plays a tumor-suppressive role and is normally quietened in GC. The downregulation of transforming growth factor-beta receptor II (TGFBR2) affects TGFβ signaling pathway, which exerts an immense effect on tumor cell proliferation and metastasis. Although the effect of the TGFβ signaling pathway on cancer cells is well studied, little is known about the mechanism by which TGFBR2 expression is downregulated. Here, we showed that TGFBR2 protein, but not TGFBR2 mRNA, was consistently downregulated in GC, suggesting that post-transcriptional mechanism is involved in the regulation of TGFBR2. Bioinformatics analysis and luciferase reporter analysis proved that miR-135b combines precisely with the 3'-UTR of TGFBR2 mRNA. EdU assays and cell migration assays respectively showed that miR-135b overexpression induced the growth and invasion of GC cells. However, the overexpression of TGFBR2 had the opposite effect. TGFBR2 acted as the direct target for miR-135b and was downregulated in gastric cancer cells. Therefore, miR-135b promotes proliferation and migration of GC cells by negatively regulating TGFBR2 expression, displaying an oncomiR effect. Altogether, this conclusive evidence supported that miR-135b mediates the progression of GC by targeting TGFBR2 and miR-135b/TGFBR2 axis can be used in future targeted therapy for GC.
Keywords: Gastric cancer; Migration; Proliferation; TGFBR2; miR-135b.