MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis.
MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis.
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DOI：
10.1136/gutjnl-2011-301846
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发表时间：
2013-09
期刊：
影响因子：
24.5
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Hur K;Toiyama Y;Takahashi M;Balaguer F;Nagasaka T;Koike J;Hemmi H;Koi M;Boland CR;Goel A
远处转移是结直肠癌（CRC）患者癌症相关死亡的主要原因。尽管microRNA-200 （miR-200）家族是人类癌症上皮-间质转化（EMT）的关键抑制剂，但miR-200成员在转移性结直肠癌发病机制中的作用尚未被研究。分析54对原发性结直肠癌和相应匹配的肝转移组织标本中miR-200家族成员的表达和甲基化状态。在结直肠癌细胞系中研究miR-200c过表达的功能分析，并分析细胞的增殖、侵袭和迁移。验证了几种miR-200c靶基因（ZEB1、ETS1和FLT1）和EMT标志物（E-cadherin和vimentin）在结直肠癌细胞系和组织标本中的表达。肝转移组织中miR-200c（原发CRC=1.31，肝转移=1.59,p=0.0014）和miR-141（原发CRC=0.14，肝转移=0.17,p=0.0234）的表达高于原发CRC，这与这些miRNAs启动子区低甲基化显著相关（原发CRC=61.2%，肝转移=46.7%,p<0.0001）。原位杂交分析显示，原发性结直肠癌组织的侵袭前沿miR-200c表达较低。转染miR-200c前体可增强CRC细胞系的细胞增殖，但减少其侵袭和迁移行为。在结直肠癌细胞系中过表达miR-200c导致假定的基因靶点表达降低，并导致E-cadherin升高和vimentin表达降低。miR-200c、靶基因和EMT标志物之间的关联在原发性crc和匹配的肝转移组织中得到了验证。miR-200c在介导EMT和结肠转移行为中发挥重要作用。其表达受表观遗传调控，miR-200c可能作为CRC患者的潜在诊断标志物和治疗靶点。
Distant metastasis is the major cause of cancer-related death in patients with colorectal cancer (CRC). Although the microRNA-200 (miR-200) family is a crucial inhibitor of epithelial-to-mesenchymal transition (EMT) in human cancer, the role of miR-200 members in the pathogenesis of metastatic CRC has not been investigated. Fifty-four pairs of primary CRC and corresponding matched liver metastasis tissue specimens were analysed for expression and methylation status of the miR-200 family members. Functional analysis of miR-200c overexpression was investigated in CRC cell lines, and cells were analysed for proliferation, invasion and migration. Expression of several miR-200c target genes (ZEB1, ETS1 and FLT1) and EMT markers (E-cadherin and vimentin) in CRC cell lines and tissue specimens was validated. Liver metastasis tissues showed higher expression of miR-200c (primary CRC=1.31 vs. liver metastasis=1.59; p=0.0014) and miR-141 (primary CRC=0.14 vs. liver metastasis=0.17; p=0.0234) than did primary CRCs, which was significantly associated with hypomethylation of the promoter region of these miRNAs (primary CRC=61.2% vs. liver metastasis=46.7%; p<0.0001). The invasive front in primary CRC tissues revealed low miR-200c expression by in situ hybridization analysis. Transfection of miR-200c precursors resulted in enhanced cell proliferation but reduced invasion and migration behaviours in CRC cell lines. Overexpression of miR-200c in CRC cell lines caused reduced expression of putative gene targets, and resulted in increased E-cadherin and reduced vimentin expression. The associations between miR-200c, target genes and EMT markers were validated in primary CRCs and matching liver metastasis tissues. miR-200c plays an important role in mediating EMT and metastatic behaviour in the colon. Its expression is epigenetically regulated, and miR-200c may serve as a potential diagnostic marker and therapeutic target for patients with CRC.
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DOI：
10.1006/bbrc.2001.5521
发表时间：
2001-09-07
影响因子：
3.1
作者：
Jiang, Y;Xu, WX;Yang, XM
通讯作者：
Yang, XM
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
29.4
作者：
Goel, Ajay;Xicola, Rosa M.;Llor, Xavier
通讯作者：
Llor, Xavier
影响因子：
4.8
作者：
Drake, Justin M.;Barnes, J. Matthew;Henry, Michael D.
通讯作者：
Henry, Michael D.
DOI：
10.1186/bcr651
发表时间：
2003
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Kowalski PJ;Rubin MA;Kleer CG
通讯作者：
Kleer CG