FOXM1-induced miR-552 expression contributes to pancreatic cancer progression by targeting multiple tumor suppressor genes.
FOXM1-induced miR-552 expression contributes to pancreatic cancer progression by targeting multiple tumor suppressor genes.
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FOXM1 诱导的 miR-552 表达通过靶向多个肿瘤抑制基因促进胰腺癌进展
DOI：
10.7150/ijbs.56733
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发表时间：
2021
影响因子：
9.2
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Wang X;Dou N;Wang J;Zhang Y;Li Y;Gao Y
microRNAs（miRNAs）的失调在肿瘤发生过程中起着重要作用。叉头盒M1（FOXM 1）是一种众所周知的致癌转录因子，与多种癌症类型的进展有关。为了找出FOXM 1在胰腺癌中诱导的异常miRNA，我们分析了TCGA数据库，并计算出miR-552是与FOXM 1最相关的miRNA。分子实验结果表明，FOXM 1通过直接结合miR-552的启动子区域来转录激活miR-552的表达。在胰腺癌组织微阵列中，miR-552表达与FOXM 1正相关，miR-552高表达可预测患者预后不良。在功能上，miR-552的过表达促进胰腺癌细胞迁移，而miR-552的抑制减弱了这种表型。外源性表达miR-552可恢复FOXM 1敲低对细胞迁移的抑制作用。通过信息学分析，我们鉴定了三个肿瘤抑制基因：DACH 1，PCDH 10和SMAD 4，它们都与FOXM 1负相关，并被验证为miR-552的功能相关靶点。总之，我们的研究结果提供了一个新的FOXM 1-miR-552-DACH 1/PCDH 10/SMAD 4轴来调节胰腺癌细胞的进展，并为针对这种疾病的治疗干预提供了新的机会。
Dysregulation of microRNAs (miRNAs) plays important roles during carcinogenesis. Forkhead box M1 (FOXM1), a well-known oncogenic transcription factor, has been implicated in the progression of multiple cancer types. To find out FOXM1-induced abnormal miRNAs in pancreatic cancer, we analyzed TCGA database and figured out miR-552 as the most relevant miRNA with FOXM1. Molecular experimental results demonstrated that FOXM1 transcriptionally activated miR-552 expression by directly binding to the promoter region of miR-552. In a pancreatic cancer tissue microarray, miR-552 expression was positively correlated with FOXM1 and high expression of miR-552 could predict poor patient outcome. Functionally, overexpression of miR-552 promoted pancreatic cancer cell migration and inhibition of miR-552 attenuated this phenotype. The inhibitory effect on cell migration caused by FOXM1 knockdown could be restored by exogenous expression of miR-552. By informatics analysis, we identified three tumor suppressor genes: DACH1, PCDH10 and SMAD4, all of which were negatively associated with FOXM1 and validated as functionally relevant targets of miR-552. Taken together, our findings provide a new FOXM1-miR-552-DACH1/PCDH10/SMAD4 axis to regulate pancreatic cancer cell progression and new opportunities for therapeutic intervention against this disease.
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11.2
作者：
Raychaudhuri P;Park HJ
通讯作者：
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影响因子：
3.7
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通讯作者：
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