MicroRNA‐155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor‐β receptor 2

• Published in: Cancer science 2018-03, Vol.109 (3), p.618-628
• Main Authors: Qu, Yajing, Zhang, Haiyang, Sun, Wu, Han, Yueting, Li, Shuang, Qu, Yanjun, Ying, Guoguang, Ba, Yi
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Animals; Cell Line, Tumor; Cell Proliferation; Down-Regulation; gastric cancer; Gene Expression Regulation, Neoplastic; growth; Humans; invasion; Mice; MicroRNAs - genetics; miR‐155; Neoplasm Invasiveness; Neoplasm Transplantation; Original; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; transforming growth factor‐β receptor 2
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13472

Gastric cancer (GC) is one of the most common malignancies worldwide and has high morbidity and mortality rates. It is essential to elucidate the molecular events of GC proliferation and invasion, which will provide new therapeutic targets for GC. The inactivation of transforming growth factor‐β receptor 2 (TGFβR2) correlates with cancer cell growth and metastasis, but the mechanisms underlying the downregulation of TGFβR2 expression remain unknown. MicroRNAs (miRNAs) act as post‐transcriptional regulators and play a key role in the development of cancers. Bioinformatics analysis and luciferase reporter assays have shown that miR‐155 directly binds to the 3′‐UTR of TGFβR2 mRNA. In this study, we found that the TGFβR2 protein levels, but not mRNA levels, were downregulated in GC tissues, and the levels of miR‐155 were significantly increased in GC tissues. We deduced that miR‐155 was inversely correlated with TGFβR2 in GC cells. In vitro studies showed that overexpression of miR‐155 in SGC7901 inhibited the expression of TGFβR2 and then promoted GC cell proliferation and migration, whereas miR‐155 inhibitor showed opposite effects. In addition, the tumor‐suppressing function of TGFβR2 was verified by using siRNA and TGFβR2 overexpressing plasmids. The results showed that miR‐155 promotes cell growth and migration by negatively regulating TGFβR2. Thus, miR‐155‐regulated TGFβR2 as a potential therapeutic target in GC. This study demonstrated for the first time that miR‐155 can target TGFβR2 to promote GC growth and invasion, and we identified the miR‐155 — TGF?R2 axis in GC.