CDK3, target of miR-4469, suppresses breast cancer metastasis via inhibiting Wnt/β-catenin pathway.
CDK3, target of miR-4469, suppresses breast cancer metastasis via inhibiting Wnt/β-catenin pathway.
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CDK3（miR-4469 的靶标）通过抑制 Wnt/β-catenin 通路抑制乳腺癌转移
DOI：
10.18632/oncotarget.18171
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发表时间：
2017-10-17
期刊：
影响因子：
--
通讯作者：
Zheng D
中科院分区：
文献类型：
--
作者：
Cao T;Xiao T;Huang G;Xu Y;Zhu JJ;Wang K;Ye W;Guan H;He J;Zheng D
细胞周期蛋白依赖性激酶3（Cyclin-dependent kinase 3，CDK 3）是CDK家族的成员之一，参与G 0/G1和G1/S细胞周期转换。虽然有研究者发现CDK 3与某些肿瘤的细胞生长有关，但CDK 3在肿瘤发生发展中的作用尚不清楚。在此，我们首次发现CDK 3在非转移性乳腺癌原发肿瘤中的表达高于转移性乳腺癌。CDK 3的过表达可以抑制乳腺癌细胞的迁移和侵袭，并减少裸小鼠的转移。我们进一步鉴定了miR-4469是CDK 3的负调控因子，它直接作用于CDK 3的3′-非翻译区（UTR）。miR-4469诱导的运动增加可被CDK 3过表达所消除。此外，RNA-seq分析显示Wnt途径可能被CDK 3表达抑制，这随后通过蛋白质印迹证实。此外，Wnt 3a处理消除了CDK 3在细胞运动中的抑制作用，表明Wnt信号传导是CDK 3的潜在下游。综上所述，这些结果支持miR-4469靶向的CDK 3通过抑制Wnt/β-catenin途径抑制乳腺癌转移。
Cyclin-dependent kinase 3 (CDK3), a member of CDK family, is involved in G0/G1 and G1/S cell cycle transitions. Although several researchers discovered that CDK3 related to cell growth in some kinds of cancer, the functions of CDK3 during tumor development remains unclear. Here, we first found that the expression of CDK3 was higher in primary tumors of non-metastatic breast cancer compared with those in metastatic breast cancer. Overexpression of CDK3 suppressed cell migration and invasion of breast cancer cells, and decreased the metastasis in nude mice. We further identified miR-4469 was a negative regulator of CDK3 by directly targeting its 3′-untranslated region (UTR). The increase of motility induced by miR-4469 could be abolished by CDK3 overexpression. Moreover, RNA-seq analysis revealed that Wnt pathway may be inhibited by CDK3 expression, which was subsequently confirmed by western blot. Moreover, Wnt3a treatment abolished the inhibitory role of CDK3 in cell motility, suggesting that Wnt signaling is the potential downstream of CDK3. In conclusion, these results support that CDK3 which is targeted by miR-4469 suppresses breast cancer metastasis by inhibiting Wnt/β-catenin pathway.
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影响因子：
8
作者：
Cui, J.;Yang, Y.;Zhang, C.
通讯作者：
Zhang, C.
影响因子：
11.2
作者：
Micalizzi DS;Wang CA;Farabaugh SM;Schiemann WP;Ford HL
通讯作者：
Ford HL
影响因子：
64.5
作者：
Ren, SJ;Rollins, BJ
通讯作者：
Rollins, BJ
DOI：
10.1046/j.0014-2956.2001.02555.x
发表时间：
2001-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Yamochi, T;Semba, K;Matsuoka, M
通讯作者：
Matsuoka, M
影响因子：
20.3
作者：
Jima, Dereje D.;Zhang, Jenny;Dave, Sandeep S.
通讯作者：
Dave, Sandeep S.