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

miR-205 regulates the proliferation and invasion of ovarian cancer cells via suppressing PTEN/SMAD4 expression.
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DOI:
10.3892/ol.2018.8313
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发表时间:
2018-05
期刊:
影响因子:
2.9
通讯作者:
Zong L
Zong L
中科院分区:
医学4区
文献类型:
--
作者:
Chu P;Liang A;Jiang A;Zong L

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microRNA(miRNAs/miRs)是一类转录后调控靶基因的非编码RNA,参与肿瘤的发生、凋亡、增殖、侵袭、转移和化疗耐药等过程。然而,关于卵巢癌中miRNA的数据仍然不完整。本研究旨在鉴定影响卵巢癌恶性表型的miRNAs,并分析其可能的作用机制。数据表明,miR-205通过抑制磷酸酶和张力蛋白同源物(PTEN)/母体抑制十肢麻痹同源物4(SMAD 4)表达来促进卵巢癌细胞的细胞增殖和侵袭。基于Cancer Genome Atlas数据库分析结果,发现miR-205在卵巢癌组织中显著上调,与卵巢癌患者的不良预后显著相关;其在卵巢癌患者组织中的异常表达也通过逆转录定量聚合酶链反应得到证实。另外的基因本体分析显示miR-205的靶基因与细胞增殖和侵袭相关。与数据库分析一致,miR-205过表达显著促进卵巢癌细胞体外增殖和侵袭。为了进一步探讨miR-205与卵巢癌细胞增殖和侵袭相关的机制,基于miR-205与增殖和侵袭相关的靶基因构建了蛋白质-蛋白质相互作用网络,发现PTEN和SMAD 4是miR-205的关键靶基因。在卵巢癌组织中,PTEN和SMAD 4的表达水平明显下调,表明miR-205可能在体内抑制PTEN和SMAD 4的表达。在体外,miR-205过表达显著抑制SMAD 4和PTEN的表达,进一步证实了PTEN和SMAD 4是miR-205在卵巢癌细胞中的靶基因。这些结果阐明了miR-205的促肿瘤作用,并确立了miR-205作为卵巢癌的潜在治疗靶点。
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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