Tumor suppressor miR-1 inhibits tumor growth and metastasis by simultaneously targeting multiple genes.
Tumor suppressor miR-1 inhibits tumor growth and metastasis by simultaneously targeting multiple genes.
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肿瘤抑制因子 miR-1 通过同时靶向多个基因抑制肿瘤生长和转移
DOI：
10.18632/oncotarget.14927
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发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Liu C;Zhang S;Wang Q;Zhang X
肿瘤的进展取决于肿瘤的生长和转移，而肿瘤的生长和转移是由多个基因激活或抑制的。一个单独的microRNA可能靶向多个基因，这表明一个miRNA可能通过同时靶向不同的基因来抑制肿瘤的生长和转移。然而，到目前为止，这个问题还没有被探讨过。在本研究中，研究结果表明miR-1可以通过靶向多个基因同时抑制胃癌和乳腺癌的生长和转移。结果表明，与正常组织相比，miR-1在癌组织中的表达显著下调。MiR-1过表达导致胃癌细胞和乳腺癌细胞的细胞周期停滞于G1期，而在正常细胞中未见。此外，miR-1过表达显著抑制了胃癌细胞和乳腺癌细胞的转移。机制分析表明，miR-1同时抑制肿瘤生长和转移是由于6个miR-1靶基因同步靶向，编码细胞周期蛋白依赖激酶4、双丝蛋白肌动蛋白结合蛋白1、降钙素3、冠状病毒1C是蛋白家族成员2和胸腺素β4，X-连锁。体内实验表明，miR-1能有效抑制胃癌和乳腺癌裸鼠移植瘤的生长和转移。因此，我们的研究对miR-1‘S在胃癌和乳腺癌发生中的作用提供了新的见解。
Cancer progression depends on tumor growth and metastasis, which are activated or suppressed by multiple genes. An individual microRNA may target multiple genes, suggesting that a miRNA may suppress tumor growth and metastasis via simultaneously targeting different genes. However, thus far, this issue has not been explored. In the present study, the findings showed that miR-1 could simultaneously inhibit tumor growth and metastasis of gastric and breast cancers by targeting multiple genes. The results indicated that miR-1 was significantly downregulated in cancer tissues compared with normal tissues. The miR-1 overexpression led to cell cycle arrest in the G1 phase in gastric and breast cancer cells but not in normal cells. Furthermore, the miR-1 overexpression significantly inhibited the metastasis of gastric and breast cancer cells. An analysis of the underlying mechanism revealed that the simultaneous inhibition of tumor growth and metastasis mediated by miR-1 was due to the synchronous targeting of 6 miR-1 target genes encoding cyclin dependent kinase 4, twinfilin actin binding protein 1, calponin 3, coronin 1C, WAS protein family member 2 and thymosin beta 4, X-linked. In vivo assays demonstrated that miR-1 efficiently inhibited tumor growth and metastasis of gastric and breast cancers in nude mice. Therefore, our study contributed novel insights into the miR-1′s roles in tumorigenesis of gastric and breast cancers.
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