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

Abstract

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.

Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

“…miRNA dysregulation has been indicated to induce cancer cell proliferation, inflammation, invasion, migration, and metastasis . Previous studies showed that miR‐155 was involved in GC‐associated inflammation, ie, miR‐155 is expressed by immune cells such as macrophages, dendritic cells, and various subsets of lymphocytes, and it affected both pro‐ and anti‐inflammation in myeloid cells and several cancers . Unfortunately, little is known about miR‐155 in GC.…”

Circular RNA hsa_circ_0001829 Promotes Gastric Cancer Progression through miR-155-5p/SMAD2 Axis

“…However, the role of miR-155-5p in GC remains contradictory and largely unclear. Li and colleagues reported that miR-155-5p is one of the most downregulated miRNAs and may serve as a tumor suppressor in GC (39), whereas Qu′s group claimed that the levels of miR-155-5p were obviously increased and miR-155-5p acts as an oncogene in GC (40). In our study, the CCK-8 and EdU assays showed that miR-155-5p mimics effectively reversed the hsa_circ_0001829-mediated promotion of GC cell proliferation, and likewise, the transwell assay showed that miR-155-5p mimics attenuated the ability of hsa_circ_0001829 to promote invasion of GC cells.…”

Clinical Significance of MicroRNA-155 Regulated Autophagy and Apoptosis by targeting gene Rictor/Fos in Gastric Cancer Progression

“…We believe that the abnormal distribution of the above cells in tumor tissues may be one of the reasons for the abnormal expression of microRNA-155. Moreover, Qu Y [23] reported that microRNA-155 is highly expressed in gastric cancer tissues; Conversely, other groups reported that microRNA-155 was poorly expressed in gastric cancer tissues [24][25][26] . To further illustrate the real role of microRNA-155 in gastric cancer, more attention should be paid on this research area.…”