miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2
miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2
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DOI：
10.2147/cmar.s220568
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Gao, Yan
中科院分区：
文献类型：
--
作者：
Cai, Yuxing;Hao, Yi;Gao, Yan
背景资料：越来越多的证据表明microRNAs（miRNAs）在非小细胞肺癌（NSCLC）的发生和发展中起着重要作用。方法：采用RT-qPCR方法检测miR-1305在NSCLC中的表达。通过细胞计数试剂盒8（CCK-8）、集落形成和流式细胞术分析来确定miR-1305对NSCLC细胞生长的影响。利用miRDB数据库预测miR-1305的靶点。进行荧光素酶报告基因测定以研究miR-1305与MDM 2的3 '-UTR之间的结合。Western blot检测miR-1305对MDM 2表达的影响。结果：miR-1305在NSCLC组织和细胞系中表达下调。miR-1305的表达与NSCLC患者的转移和预后不良显著相关。miR-1305过表达可抑制NSCLC细胞的增殖和迁移，促进细胞凋亡。生物信息学和荧光素酶检测发现小鼠/小鼠双微体2（MDM 2）是miR-1305的靶点。miR-1305结合MDM 2的3 '-非翻译区（UTR）并降低NSCLC细胞中MDM 2的表达。由于MDM 2是p53的负调控因子，因此通过miR-1305降低MDM 2可上调NSCLC细胞中p53的丰度。结论：本研究为miR-1305/MDM 2信号通路调控NSCLC的进展提供了新的机制，提示miR-1305是一个有希望的NSCLC治疗靶点。
Background: Increasing evidence has suggested the critical implication of microRNAs (miRNAs) in the initiation and progression of non-small cell lung cancer (NSCLC). Previous studies have shown the tumor-suppressive function of miR-1305 in cancer; however, the role of miR-1305 in NSCLC has not been fully understood.Methods: The expression of miR-1305 in NSCLC was detected by RT-qPCR. The influence of miR-1305 on the growth of NSCLC cells was determined via Cell Counting Kit 8 (CCK-8), colony formation and FACS analysis. The targets of miR-1305 were predicted with the miRDB database. Luciferase reporter assay was performed to investigate the binding between miR-1305 and 3'-UTR of MDM2. Western blot was applied to check the expression of MDM2 with miR-1305.Results: Here, we found that miR-1305 was down-regulated in NSCLC tissues and cell lines. Decreased miR-1305 was significantly correlated with the metastasis and poor prognostics of NSCLC patients. Overexpression of miR-1305 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Bioinformatics and luciferase assay uncovered that the mouse/murine double minute 2 (MDM2) was a target of miR-1305. miR-1305 bound the 3'-untranslated region (UTR) of MDM2 and decreased the expression of MDM2 in NSCLC cells. As MDM2 was a negative regulator of p53, decreased MDM2 by miR-1305 up-regulated the abundance of p53 in NSCLC cells. Restoration of MDM2 markedly attenuated the suppressive role of miR-1305 in the proliferation and migration of NSCLC cells.Conclusion: The findings provided novel mechanism of miR-1305/MDM2 signaling in regulating the progression of NSCLC, suggesting miR-1305 as a promising target for the treatment of NSCLC.