miR-139-5p Inhibits the Epithelial-Mesenchymal Transition and Enhances the Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating BCL2.
miR-139-5p Inhibits the Epithelial-Mesenchymal Transition and Enhances the Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating BCL2.
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miR-139-5p通过下调BCL2抑制上皮-间质转化并增强结直肠癌细胞的化疗敏感性
DOI：
10.1038/srep27157
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发表时间：
2016-05-31
影响因子：
4.6
通讯作者：
Cai G
中科院分区：
文献类型：
--
作者：
Li Q;Liang X;Wang Y;Meng X;Xu Y;Cai S;Wang Z;Liu J;Cai G
microRNA（miRNAs）是参与包括结直肠癌（CRC）在内的多种癌症的重要调节因子。参与CRC进展和转移的miRNA的功能和机制在很大程度上是未知的。本研究通过miRNA微阵列技术筛选与结直肠癌进展相关的关键miRNA，并选择miR-139- 5 p作为研究对象。通过CCK-8增殖测定、细胞侵袭和迁移、细胞凋亡和KO小鼠研究证实了miR-139- 5 p在结肠癌中的功能作用。与正常组织相比，癌组织中miR-139- 5 p的表达显著降低。miR-139- 5 p表达水平与肿瘤分期有关（P< 0.01）。功能研究显示，miR-139- 5 p通过影响上皮间质转化（EMT），与结肠癌细胞的转移潜能和耐药性显著相关。然后，我们在体外鉴定BCL 2为miR-139- 5 p细胞的直接靶点。患者样本和KO小鼠模型显示BCL 2表达与miR-139- 5 p表达呈负相关。总之，我们发现miR-139- 5 p靶向BCL 2通路，以降低CRC的肿瘤转移和药物敏感性。该轴提供了深入了解CRC转移的miRNA调控机制和CRC治疗的新治疗靶点。
MicroRNAs (miRNAs) are important regulators involved in various cancers, including colorectal cancer (CRC). The functions and mechanisms of the miRNAs involved in CRC progress and metastasis are largely unknown. In this study, miRNA microarray analysis was performed to screen crucial miRNAs involved in CRC progress and miR-139-5p was chosen for further study. The functional roles of miR-139-5p in colon cancer were demonstrated by CCK-8 proliferation assay, cell invasion and migration, cell apoptosis and in a KO mouse study. miR-139-5p expression was significantly decreased in cancer tissues compared to normal tissues. The miR-139-5p expression level was associated with tumour stage (P< 0.01). Function studies revealed that miR-139-5p was significantly correlated with the metastasis potential and drug resistance of colon cancer cells by affecting the epithelial-mesenchymal transition (EMT). Then, we identified BCL2 as a direct target of miR-139-5p cellsin vitro. The patient samples and KO mice model showed that BCL2 expression was inversely correlated with the expression of miR-139-5p. In conclusion, we found that miR-139-5p targeted the BCL2 pathway to reduce tumour metastasis and drug sensitivity in CRC. This axis provided insight into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC therapy.