ABSTRACT
BACKGROUND/AIMS: MicroRNA (miRNA) plays important roles in the development of different cancers. In this study, we investigated the roles and mechanisms of miR-203 in human cervical cancer. METHODS: miR-203 expression was detected in cervical cancer tumors and cell lines by qRT-PCR. The methylation status in the promoter region of miR-203 was examined by methylation-specific PCR. The functional effect of miR-203 was determined by both in vitro and in vivo assays. RESULTS: miR-203 was frequently down-regulated in cervical cancer tumors and cell lines. This down-regulation of miR-203 was associated with methylation of the miR-203 promoter. Furthermore, miR-203 down-regulated vascular endothelial growth factor alpha (VEGFA) expression by directly targeting its 3'-untranslated region. Functional assays revealed that miR-203 suppressed cervical cancer cell proliferation, tumor growth, and angiogenesis in nude mice, whereas forced expression of VEGFA rescued this inhibitory effect. CONCLUSION: Our collective findings indicate that miR-203 functions as a tumor suppressor by targeting VEGFA, resulting in the inhibition of tumor growth and angiogenesis. Thus, miR-203 may be a potential therapeutic target and prognostic marker in cervical cancer.
Subject(s)
MicroRNAs/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , 3' Untranslated Regions , Animals , Base Sequence , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Down-Regulation , Female , HeLa Cells , Humans , Mice , Mice, Nude , MicroRNAs/genetics , Neovascularization, Pathologic , Promoter Regions, Genetic , Transplantation, Heterologous , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: [corrected] microRNAs (miRNAs) are involved in cancer-related processes. The miRNA-125b (miR-125b) has been identified as miRNA over-expressed in a wide variety of cancers. However, the role of miR-125b in the context of cervical carcinoma remains unknown. METHODS: In this study, the effect of miR-125b on the proliferation and apoptosis of human cervical cells was analyzed by MTT assay and Flow cytometry analysis. we identified phosphoinositide 3-kinase catalytic subunit delta (PIK3CD) as a novel miR-125b target. RESULTS: overexpression of miR- 125b in HeLa cervical cancer cells decreased cell proliferation, induced apoptosis and down-regulated expression of PIK3CD. To identify the mechanisms responsible, we investigated the PI3K/Akt pathway and found that PI3K, phospho-Akt, and phospho-mTOR were all down-regulated, while Bid was up-regulated in miR-125b-overexpressing subclones. In vivo, over expression of miR-125b in HeLa cells markedly reduced their ability to form tumors. CONCLUSION: these results suggest that miR-125b suppresses tumor growth activity by targeting the PI3K/ Akt/mTOR signaling pathway, and may provide a target for effective therapies.
