The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.
The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.
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FOXD3/miR-214/MED19 轴抑制人结直肠癌的肿瘤生长和转移
DOI：
10.1038/bjc.2016.362
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发表时间：
2016-11-22
影响因子：
8.8
通讯作者：
Liang, L.
中科院分区：
文献类型：
--
作者：
He, G. Y.;Hu, J. L.;Zhou, L.;Zhu, X. H.;Xin, S. N.;Zhang, D.;Lu, G. F.;Liao, W. T.;Ding, Y. Q.;Liang, L.
MiR-214在几种肿瘤中受到异常调节，但其在结直肠癌（CRC）转移中的潜在机制仍不清楚。方法：采用生物信息学方法预测miR-214的转录因子和靶点，并采用ChIP和双荧光素酶报告基因技术进行验证。采用亚硫酸氢盐测序PCR检测DNA甲基化状态。采用MTT法、平板集落形成法、Matrigel侵袭法和动物模型评价miR-214在结直肠癌中的体内外功能。结果：miR-214在结直肠癌组织中表达下调，与结直肠癌淋巴结转移密切相关。miR-214在结直肠癌中的表达下调可能是由于其启动子甲基化所致。通过ChIP分析验证FOXD 3是miR-214的转录因子。双荧光素酶试验鉴定MED 19为CRC中miR-214的靶点。体内外实验表明，miR-214通过靶向MED 19介导FOXD 3对细胞增殖、侵袭和转移的抑制作用。斯皮尔曼相关分析显示，FOXD 3与miR-214在大肠癌细胞和临床标本中呈正相关，FOXD 3与MED 19、miR-214与MED 19呈负相关。靶向miR-214介导的轴可能有助于CRC的治疗。
Background:MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC.Methods:The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens.Results:MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman’s correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens.Conclusions:FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.
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破骨细胞来源的外泌体 miR-214-3p 抑制成骨细胞骨形成
影响因子：
16.6
作者：
Li D;Liu J;Guo B;Liang C;Dang L;Lu C;He X;Cheung HY;Xu L;Lu C;He B;Liu B;Shaikh AB;Li F;Wang L;Yang Z;Au DW;Peng S;Zhang Z;Zhang BT;Pan X;Qian A;Shang P;Xiao L;Jiang B;Wong CK;Xu J;Bian Z;Liang Z;Guo DA;Zhu H;Tan W;Lu A;Zhang G
通讯作者：
Zhang G
FoxD3 调节的 microRNA-137 通过靶向 AKT2 抑制人肝细胞癌的肿瘤生长和转移
影响因子：
--
作者：
Liu LL;Lu SX;Li M;Li LZ;Fu J;Hu W;Yang YZ;Luo RZ;Zhang CZ;Yun JP
通讯作者：
Yun JP
影响因子：
3.1
作者：
Ioshikhes, Ilya;Roy, Sashwati;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
3.4
作者：
Liu, Yingtao;Tao, Xiang;Feng, Youji
通讯作者：
Feng, Youji
影响因子：
--
作者：
Bier A;Giladi N;Kronfeld N;Lee HK;Cazacu S;Finniss S;Xiang C;Poisson L;deCarvalho AC;Slavin S;Jacoby E;Yalon M;Toren A;Mikkelsen T;Brodie C
通讯作者：
Brodie C