MiR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer

• Published in: FEBS letters 2014-04, Vol.588 (7), p.1168-1177
• Main Authors: Qiu, Tianzhu, Zhou, Xin, Wang, Jian, Du, Yiping, Xu, Jun, Huang, Zebo, Zhu, Wei, Shu, Yongqian, Liu, Ping
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Binding Sites; Cell Cycle Checkpoints; Cell cycle progression; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Gastric cancer; Gene Expression Regulation, Neoplastic; Humans; Invasion; MicroRNAs - genetics; Migration; miR-133a; miR-133b; miR-145; Neoplasm Invasiveness; Proliferation; RNA Interference; Sp1; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.02.054

•miR-145, miR-133a and miR-133b were down-regulated in gastric cancer cell lines and tissues.•miR-145, miR-133a and miR-133b induced G1 cell cycle arrest and inhibited cell proliferation, migration and invasion in gastric cancer cells.•SP1 was identified as target of miR-145, miR-133a and miR-133b and negatively regulated by miR-145, miR-133a and miR-133b.•MiR-145, miR-133a and miR-133b down-regulate the expression of MMP-9 and Cyclin D1 via decreasing Sp1 expression in gastric cancer cells. MicroRNAs have recently emerged as key regulators of gastric cancers. Here we found that miR-145, miR-133a and miR-133b were down-regulated in gastric cancer tissues and cell lines. Overexpression of miR-145, miR-133a and miR-133b induced G1 cell cycle arrest and inhibited cell proliferation, migration and invasion in vitro. MiR-145, miR-133a and miR-133b targeted the transcription factor SP1, knockdown of which reduced the expression of MMP-9 and Cyclin D1 that were involved in cell growth and invasion. Thus, our findings demonstrated for the first time that miR-145, miR-133a and miR-133b suppressed the proliferation, migration, invasion and cell cycle progression of gastric cancer cells through decreasing expression of Sp1 and its downstream proteins.