MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2

BACKGROUND: Accumulating studies have demonstrated that high-mobility group A2 (HMGA2), an oncofetal protein, plays a role in tumor development and progression. However, the molecular role of HMGA2 in ovarian carcinoma is yet to be established. MicroRNAs (miRNAs), a group of small noncoding RNAs, negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. The aim of this study was to investigate the potential involvement of a specific miRNA, miR-219-5p, in HMGA2-induced ovarian cancer. METHODS: The ovarian cancer cell line, SKOV3, was employed, and miR-219-5p and HMGA2 overexpression vectors constructed. The CCK-8 kit was used to determine cell proliferation and the Transwell® assay used to measure cell invasion and migration. RT-PCR and western blot analyses were applied to analyze the expression of miR-219-5p and HMGA2, and the luciferase reporter assay used to examine the interactions between miR-219-5p and HMGA2. Nude mice were employed to characterize in vivo tumor growth regulation. RESULTS: Expression of miR-219-5p led to suppression of proliferation, invasion and migration of the ovarian cancer cell line, SKOV3, by targeting HMGA2. The inhibitory effects of miR-219-5p were reversed upon overexpression of HMGA2. Data from the luciferase reporter assay showed that miR-219-5p downregulates HMGA2 via direct integration with its 3'-UTR. Consistent with in vitro findings, expression of miR-219-5p led to significant inhibition of tumor growth in vivo. CONCLUSION: Our results collectively suggest that miR-219-5p inhibits tumor growth and metastasis by targeting HMGA2.

Effect of miR-219-5p on malignant phenotype of glioblastoma cells / 肿瘤

Objective: To investigate the effect of miR-219-5p on malignant phenotype of glioblastoma cells involving proliferation, apoptosis and invasion, and to preliminarily determine the candidate target genes of miR-219-5p related to the inhibition of cancer. Methods: The inverse relationship between mRNAs and miR-219-5p in glioblastoma tissues from sixty cases was obtained by analysis of miR-219- 5p expression level and mRNA expression profiling. DAVID software for functional analysis was employed to analyze the functions of the top 50 mRNAs and screen out two sets of mRNAs related to glioblastoma progression. The target genes of miR-219-5p were screened out from the two sets of miRNAs on four websites of online target-binding prediction. MTT assay, flow cytometry (FCM) assay and Transwell assay were performed to detect the effects of miR-219-5p on the proliferation, apoptosis and invasion of human glioblastoma cells, respectively. Results: Fourteen proliferation/apoptosis-related genes and five invasion-related genes were screened from glioblastoma tissues of sixty patients (P <0.001). Four genes including TWIST 1, MYO 1B , WEE 1 and SPRED 2 were predicted as potential target genes of miR-219-5p from 19 candidate genes. Functional analysis revealed that miR-219-5p could suppress the proliferation and invasion of glioblastoma cells as well as promote the apoptosis (P <0.05). Conclusion: MiR-219-5p may suppress the malignant phenotype of glioblastoma cells through multiple gene targets. © 2012 by Tumor.