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.

胃癌（GC）是全世界常见的恶性肿瘤，发病率高且生存率低。转化生长因子-β（TGFβ）信号转导通路通常起着肿瘤抑制作用，通常在GC中被沉默。转化生长因子-β受体II（TGFBR2）的下调影响TGFβ信号传导途径，这对肿瘤细胞的增殖和转移产生巨大影响。尽管已充分研究了TGFβ信号通路对癌细胞的作用，但对TGFBR2表达下调的机制知之甚少。在这里，我们显示了TGFBR2蛋白而不是TGFBR2 mRNA在GC中始终被下调，这表明转录后机制参与了TGFBR2的调节。生物信息学分析和荧光素酶报告基因分析证明，miR-135b与TGFBR2 mRNA的3'-UTR精确结合。EdU分析和细胞迁移分析分别表明miR-135b过表达诱导GC细胞的生长和侵袭。但是，TGFBR2的过表达具有相反的作用。TGFBR2充当miR-135b的直接靶标，并在胃癌细胞中下调。因此，miR-135b通过负调节TGFBR2的表达来促进GC细胞的增殖和迁移，表现出oncomiR效应。总之，这一确凿的证据支持miR-135b通过靶向TGFBR2介导GC的进程，并且miR-135b / TGFBR2轴可用于将来的GC靶向治疗。EdU分析和细胞迁移分析分别表明miR-135b过表达诱导GC细胞的生长和侵袭。但是，TGFBR2的过表达具有相反的作用。TGFBR2充当miR-135b的直接靶标，并在胃癌细胞中下调。因此，miR-135b通过负调节TGFBR2的表达来促进GC细胞的增殖和迁移，表现出oncomiR效应。总之，这一确凿的证据支持miR-135b通过靶向TGFBR2介导GC的进程，并且miR-135b / TGFBR2轴可用于将来的GC靶向治疗。EdU分析和细胞迁移分析分别表明miR-135b过表达诱导GC细胞的生长和侵袭。但是，TGFBR2的过表达具有相反的作用。TGFBR2充当miR-135b的直接靶标，并在胃癌细胞中下调。因此，miR-135b通过负调节TGFBR2的表达来促进GC细胞的增殖和迁移，表现出oncomiR效应。总之，这一确凿的证据支持miR-135b通过靶向TGFBR2介导GC的进程，并且miR-135b / TGFBR2轴可用于将来的GC靶向治疗。miR-135b通过负调节TGFBR2的表达来促进GC细胞的增殖和迁移，表现出oncomiR效应。总之，这一确凿的证据支持miR-135b通过靶向TGFBR2介导GC的进程，并且miR-135b / TGFBR2轴可用于将来的GC靶向治疗。miR-135b通过负调节TGFBR2的表达来促进GC细胞的增殖和迁移，表现出oncomiR效应。总之，这一确凿的证据支持miR-135b通过靶向TGFBR2介导GC的进程，并且miR-135b / TGFBR2轴可用于将来的GC靶向治疗。