Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma.
Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma.
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DOI：
10.3892/ijo.2013.2145
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发表时间：
2013-12
影响因子：
5.2
通讯作者：
Seki N
中科院分区：
文献类型：
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作者：
Yamamoto N;Kinoshita T;Nohata N;Yoshino H;Itesako T;Fujimura L;Mitsuhashi A;Usui H;Enokida H;Nakagawa M;Shozu M;Seki N
我们最近对microRNA(MiRNA)表达特征的研究表明，microRNA-29a(miR-29a)在几种类型的人类癌症中显著下调，表明miR-29a可能是人类癌症中一种可能的肿瘤抑制miRNA。本研究的目的是探讨miR-29a在宫颈鳞癌中的功能意义，寻找miR-29a调控的新的肿瘤通路和参与宫颈鳞癌发生和转移的靶基因。对宫颈癌细胞系CaSKi、HeLa、ME180和Yumoto的miR-29a修复实验表明，miR-29a能显著抑制癌细胞的迁移和侵袭。基因表达数据和计算机分析表明，热休克蛋白47(HSP47)是丝氨酸蛋白酶抑制剂超家族中的一员，也是参与胶原分子成熟的分子伴侣，是miR-29a调控的潜在靶点。荧光素酶报告分析表明miR-29a直接调控HSP47。此外，HSP47基因的沉默显著抑制了癌细胞的迁移和侵袭，免疫组化显示HSP47在癌组织和宫颈上皮内瘤变(CIN)中的表达上调。MiR-29a的下调在宫颈鳞癌中是常见的事件，miR-29a通过直接靶向HSP47而发挥肿瘤抑制作用。对抑制肿瘤的miRNA调控的分子靶点的识别为深入了解宫颈鳞癌的发生和转移的潜在机制提供了新的见解，并为治疗这种疾病提供了新的治疗策略。
Our recent studies of microRNA (miRNA) expression signatures indicated that microRNA-29a (miR-29a) was significantly downregulated in several types of human cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of miR-29a in cervical squamous cell carcinoma (SCC) and to identify novel miR-29a-regulated cancer pathways and target genes involved in cervical SCC oncogenesis and metastasis. Restoration of miR-29a in cervical cancer cell lines (CaSKi, HeLa, ME180 and Yumoto) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that heat-shock protein 47 (HSP47), a member of the serpin superfamily of serine proteinase inhibitors and a molecular chaperone involved in the maturation of collagen molecules, was a potential target of miR-29a regulation. Luciferase reporter assays showed that miR-29a directly regulated HSP47. Moreover, silencing of the HSP47 gene significantly inhibited cell migration and invasion in cancer cells and the expression of HSP47 was upregulated in cancer tissues and cervical intraepithelial neoplasia (CIN), as demonstrated by immunostaining. Downregulation of miR-29a was a frequent event in cervical SCC and miR-29a acted as a tumor suppressor by directly targeting HSP47. Recognition of tumor-suppressive miRNA-regulated molecular targets provides new insights into the potential mechanisms of cervical SCC oncogenesis and metastasis and suggests novel therapeutic strategies for treatment of this disease.
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影响因子：
8.8
作者：
Kojima, S.;Chiyomaru, T.;Kawakami, K.;Yoshino, H.;Enokida, H.;Nohata, N.;Fuse, M.;Ichikawa, T.;Naya, Y.;Nakagawa, M.;Seki, N.
通讯作者：
Seki, N.
影响因子：
3.5
作者：
Nagai, N;Tetuya, Y;Nagata, K
通讯作者：
Nagata, K
影响因子：
5.1
作者：
Hubmacher D;Apte SS
通讯作者：
Apte SS
DOI：
10.1165/rcmb.2007-0071oc
发表时间：
2008-01-01
影响因子：
6.4
作者：
Shintani, Yasushi;Maeda, Masato;Wheelock, Margaret J.
通讯作者：
Wheelock, Margaret J.
影响因子：
8.8
作者：
通讯作者：
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