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.

miR-219 regulates PRKCI expression in tongue squamous cell carcinoma / 实用肿瘤学杂志

Objective The objective of this study were to investigate the effects of miR-219 on cell proliferation,invasion and metastasis and the correlation between PRKCI and miR-219 expression in tongue squamous cell carcinoma. Methods The lu-ciferase reporter gene assay was used to verify the predicted target gene. The expression of PRKCI in tongue squamous cell carcinoma cells overexpressed exogenous miR-219 was detected by qRT-PCR and Western blot. Finally,the reverse effects of PRKCI on the proliferation,clone formation,migration and invasion ability were examined in stable overexpressing miR-219 tongue squamous cell carcinoma(TSCC)cells by MTT assay,cell plate cloning assay,scratch assay and Transwell chamber assays. qRT-PCR assay was used to determine the expression of PRKCI gene and miR-219 in tongue squamous cell carcinoma tissues,and the relationship be-tween PRKCI and miR-219 was further analyzed. Results The bioinformatics analysis predicted that the downstream target gene of miR-219 was PRKCI. The double luciferase reporter gene assay showed that miR-219 was able to reduce the fluorescence activity of the wild type PRKCI reporter vector. In addition,qRT-PCR and Western blot also showed that miR-219 could down-regulate the expression of PRKCI in TSCC cells. MTT results showed that overexpression of PRKCI could reverse the inhibitory effect of miR-219 on the proliferation of TSCC cells,and further demonstrated that the overexpression of PRKCI could reverse the inhibitory effect of miR-219 on the proliferation, invasion and metastasis of TSCC cells by cell plate cloning, scratch and Transwell experiments. Conclusion MiR-219 plays a role in inhibiting tumor by directly targeting PRKCI and negatively regulating the expression of PRK-CI. miR-219 was negatively correlated with PRKCI expression in tongue squamous cell carcinoma.

Expression and significance of miR-219 in tongue squamous cell carcinoma / 实用肿瘤学杂志

Objective To investigate the expression of miR -219 and its role in tongue squamous cell carcinoma(TSCC).Methods The relative expression of miR -219 in the 26 samples of surgically resected paired TSCC and normal tumor -adjacent tissues was detected by qRT -PCR.The expression of miR -219 in SCC-15 and normal oral mucosa cell were also tested by qRT -PCR.The miR-219 mimic was transferred into SCC-15 cell.Cell proliferative rate and the ability of colony formation were analyzed .The abilities of migration and invasion in SCC-15 cell were evaluated by Transwell test .Results Expression of miR -219 was signifi-cantly lower in TSCC tissues(P<0.001)and SCC-15(P<0.05)in comparison with normal tumor adjacent tis-sues and normal oral mucosa cell.The abilities of proliferation(P<0.05),colony formation(P<0.05),migratio-nand invasion(P<0.05)were inhibited in miR-219-transferred SCC-15 cells.Conclusion The expression of miR-219 was downregulated in TSCC .The miR-219 could inhibit cell proliferation ,colony formation ,migra-tion and invasion in TSCC .

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.