ABSTRACT
Increasing studies have shown that MicroRNAs (miRNAs) play critical roles in the progression of lung carcinoma. In the present study, the expression and functions of miR-570 were investigated. We found that miR-570 was significantly up-regulated in lung cancer tissues, compared with adjacent non-cancerous tissues. In vitro studies further showed that miR-570 mimics could promote, while its antisense oligos inhibit cell proliferation and invasion. At the molecular level, krüppel-like factor 9 (KLF9), a tumor suppressor gene, was identified as a potential target of miR-570 in lung cancer cells. Indeed, miR-570 could negatively regulate protein levels of KLF9 through targeting its 3'-untranslated region. Taken together, our results suggest a previously unknown miR-570/KLF9 molecular network controlling lung carcinoma progression.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Cell Proliferation , Kruppel-Like Transcription Factors/metabolism , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Kruppel-Like Transcription Factors/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , Neoplasm Invasiveness , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/metabolism , Signal Transduction , Transfection , Up-RegulationABSTRACT
BACKGROUND: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. MATERIALS AND METHODS: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. RESULTS: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. CONCLUSIONS: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.
