MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer.
MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer.
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DOI：
10.1038/bjc.2013.676
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发表时间：
2014-01-07
影响因子：
8.8
通讯作者：
Matsubara, H.
中科院分区：
文献类型：
--
作者：
Akanuma, N.;Hoshino, I.;Akutsu, Y.;Murakami, K.;Isozaki, Y.;Maruyama, T.;Yusup, G.;Qin, W.;Toyozumi, T.;Takahashi, M.;Suito, H.;Hu, X.;Sekino, N.;Matsubara, H.
FSCN1 和基质金属蛋白酶 14 (MMP14) 都是侵袭伪足相关蛋白。我们在此阐明这些蛋白质的致瘤性并鉴定食管鳞状细胞癌（ESCC）的新治疗剂。通过免疫组织化学和定量 PCR 评估 FSCN1 和 MMP14，并通过 PCR 评估手术 ESCC 标本中的 microRNA (miR)-133a。 FSCN1、MMP14 和 miR-133a 在 ESCC 细胞中的作用已得到证实。根据免疫组织化学的多变量分析，FSCN1 或 MMP14 的表达是一个独立的不良预后因素，并且它们的共表达与所有检查因素中最差的总生存期 (OS) 相关。此外，它们的 mRNA 与手术标本中的 miR-133a 显着相关且均呈负相关。转染 miR-133a 模拟物可降低 ESCC 细胞中 FSCN1 和 MMP14 的 mRNA 和蛋白水平。 FSCN1 或 MMP14 的敲低以及 miR-133a 模拟物的转染抑制了 ESCC 细胞的增殖和侵袭。 miR-133a 表达较低的患者的 OS 明显低于表达较高的患者。 FSCN1 和 MMP14 的联合表达与不良预后相关，而调节其 mRNA 的 miR-133a 可以作为 ESCC 的强大肿瘤抑制因子。
FSCN1 and matrix metalloproteinase 14 (MMP14) are both invadopodia-related proteins. We herein elucidate the tumourigenicity of these proteins and identify novel therapeutic agents in esophageal squamous cell carcinoma (ESCC). FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also evaluated by PCR in surgical ESCC specimens. The roles of FSCN1, MMP14 and miR-133a were established in ESCC cells. The expression of FSCN1 or MMP14 was an independent poor prognostic factor according to a multivariate analysis of immunohistochemistry, and their co-expression correlated with the poorest overall survival (OS) out of all the examined factors. Additionally, their mRNAs significantly correlated and both inversely correlated with miR-133a in surgical specimens. Transfection of a miR-133a mimic decreased the mRNA and protein levels of both FSCN1 and MMP14 in ESCC cells. The knockdown of FSCN1 or MMP14 and transfection of a miR-133a mimic inhibited the proliferation and invasion of ESCC cells. Patients with a lower miR-133a expression have a significantly poorer OS than those with a higher expression. The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC.
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DOI：
10.1038/nrm3141
发表时间：
2011-06-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Al-Alwan M;Olabi S;Ghebeh H;Barhoush E;Tulbah A;Al-Tweigeri T;Ajarim D;Adra C
通讯作者：
Adra C
影响因子：
3.7
作者：
Gomes CP;Cho JH;Hood L;Franco OL;Pereira RW;Wang K
通讯作者：
Wang K
影响因子：
3.3
作者：
Li, Xiao-Yan;Ota, Ichiro;Weiss, Stephen J.
通讯作者：
Weiss, Stephen J.
影响因子：
4.8
作者：
D'Alessio, Silvia;Ferrari, Giovanni;Mignatti, Paolo
通讯作者：
Mignatti, Paolo