MicroRNA-29a inhibits cell migration and invasion via targeting Roundabout homolog 1 in gastric cancer cells

• Published in: Molecular medicine reports Vol. 12; no. 3; pp. 3944 - 3950
• Main Authors: LIU, XUETING, CAI, JUN, SUN, YANJUN, GONG, RENHUA, SUN, DENGQUN, ZHONG, XINGGUO, JIANG, SHITAO, HE, XINMIAO, BAO, ENWU, YANG, LIUSHENG, LI, YONGXIANG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.09.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: 3' Untranslated Regions; Adult; Aged; Alzheimer's disease; Angiogenesis; Base Sequence; Bioinformatics; Care and treatment; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Comparative analysis; Down-Regulation; Female; Gastric cancer; Genes; Genes, Reporter; Genetic aspects; Health aspects; Humans; invasion; Invasiveness; Kinases; Male; Metastasis; MicroRNA; microRNA-29a; MicroRNAs; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; migration; miRNA; mRNA; Mutation; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Protein expression; Proteins; Real-Time Polymerase Chain Reaction; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Roundabout 1; Roundabout Proteins; Sequence Alignment; siRNA; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Vascular endothelial growth factor; Western blotting; China; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2015.3817

Deregulation of Roundabout homolog 1 (Robo1) has been demonstrated to be associated with several types of human cancer, including gastric cancer. However, the detailed role of Robo1 and its regulatory mechanism in gastric cancer remain largely unclear. In the current study, it was demonstrated that the expression of microRNA (miR)-29a was frequently reduced in gastric cancer tissues, compared with their matched normal adjacent tissues. Similar results were additionally observed in AGS and SGC-7901 human gastric cancer cells. Overexpression of miR-29a led to reduced migration and invasion of AGS cells. To explore the targets of miR-29a in gastric cancer, bioinformatics analysis was conducted and Robo1 was identified as a putative target of miR-29a. Further western blotting and luciferase activity assay data confirmed that miR-29a was able to negatively regulate the protein expression of Robo1, through directly binding to the 3′-untranslated region of Robo1 mRNA in gastric cancer cells. In addition, it was demonstrated that Robo1 was frequently upregulated in gastric cancer tissues compared with their matched adjacent normal tissues, and a significant inverse correlation was identified between miR-29a and Robo1 expression. In addition, knockdown of Robo1 by small interfering RNA markedly inhibited the migratory and invasive capabilities of AGS cells, which the results obtained with overexpression of miR-29a. In conclusion, to the best of our knowledge the current study suggested for the first time, that miR-29a inhibits migration and invasion in part via direct inhibition of Robo1 in gastric cancer cells. Therefore, Robo1 and miR-29a may serve as diagnostic or therapeutic targets for gastric cancer.