miR-205 regulates the proliferation and invasion of ovarian cancer cells via suppressing PTEN/SMAD4 expression

miR-205通过抑制PTEN/SMAD4表达调控卵巢癌细胞增殖和侵袭

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作者:Ping Chu, Aihua Liang, Aili Jiang, Lu Zong

Abstract

MicroRNAs (miRNAs/miRs) are non-coding RNAs that post-transcriptionally control target genes, and are involved in tumorigenesis, apoptosis, proliferation, invasion, metastasis and chemoresistance. However, data concerning miRNAs in ovarian cancer remain incomplete. The present study aimed to identify miRNAs that affected the malignant phenotype of ovarian cancer, and to analyze their potential mechanisms. The data demonstrated that miR-205 promoted cell proliferation and invasion of ovarian cancer cells via suppressing Phosphatase and tensin homolog (PTEN)/mothers against decapentaplegic homolog 4 (SMAD4) expression. Based on the Cancer Genome Atlas database analysis results, it was identified that miR-205 was significantly upregulated in ovarian cancer tissues and markedly correlated with poor prognosis in patients with ovarian cancer; its abnormal expression was also confirmed in tissues from patients with ovarian cancer by reverse transcription quantitative polymerase chain reaction. Additional Gene Ontology analysis revealed that the target genes of miR-205 were associated with cell proliferation and invasion. Consistent with the database analysis, miR-205 overexpression significantly promoted ovarian cancer cell proliferation and invasion in vitro. To additionally explore the mechanism by which miR-205 was associated with proliferation and invasion of ovarian cancer cells, a protein-protein interaction network was constructed based on miR-205 target genes associated with proliferation and invasion, and it was revealed that PTEN and SMAD4 were key target genes of miR-205. In ovarian cancer tissues, the expression levels of PTEN and SMAD4 were significantly downregulated, suggesting that miR-205 may suppress the expression of PTEN and SMAD4 in vivo. In vitro, miR-205 overexpression markedly suppressed the expression of SMAD4 and PTEN, additionally verifying that PTEN and SMAD4 were the target genes of miR-205 in ovarian cancer cells. These results elucidated the tumor-promoting role of miR-205 and established miR-205 as a potential treatment target for ovarian cancer.

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