SNHG3 promotes migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the miR-186-5p/ZEB1 axis.
SNHG3 promotes migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the miR-186-5p/ZEB1 axis.
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发表时间：
2021
影响因子：
2.2
通讯作者：
Qun Wan;M. Tang;Shilei Sun;Jing-Bo Hu;Zi-jiu Sun;Yu-ting Fang;T. He;Yan Zhang
中科院分区：
文献类型：
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作者：
Qun Wan;M. Tang;Shilei Sun;Jing-Bo Hu;Zi-jiu Sun;Yu-ting Fang;T. He;Yan Zhang
越来越多的证据表明，长的非编码RNA(LncRNAs)参与乳腺癌的发生发展。据报道，lncRNA小核仁RNA宿主基因3(SNHG3)在肝细胞癌和结直肠癌中起癌基因作用，但对SNHG3在乳腺癌中的生物学功能和致癌机制知之甚少。我们发现SNHG3在乳腺癌组织和细胞中异常高表达，并且SNHG3的转基因表达促进了乳腺癌细胞系(MCF-7和MDA-MB-231)的增殖、迁移和侵袭。SNHG3基因敲除的MCF-7细胞移植瘤的平均体积低于对照肿瘤细胞。此外，锌指E盒结合同源盒1(ZEB1)在SNHG3过表达后表达增加，反之亦然。ZEB1的过表达引发了细胞的迁移和侵袭行为。对这些作用机制的分析表明，SNHG3是miR-186-5P的有效宿，并调节ZEB1抑制，为其转录后调控提供了一个额外的水平。综上所述，SNHG3通过调节miR-186-5p/ZEB1和诱导上皮细胞向间充质细胞转化，促进乳腺癌细胞的迁移和侵袭，提示SNHG3是乳腺癌的潜在治疗靶点。
Increasing evidence suggests that the long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. The lncRNA small nucleolar RNA host gene 3 (SNHG3) reportedly acts as an oncogene in hepatocellular carcinoma and colorectal cancer; however, little is known about the biological function and oncogenic mechanisms of SNHG3 in breast cancer. We demonstrated that the expression of SNHG3 was abnormally high in breast cancer tissues and cells, and transgenic expression of SNHG3 promoted the proliferation, migration, and invasion of breast cancer cell lines (MCF-7 and MDA-MB-231). The mean volume of the xenografts from the SNHG3-knockdown MCF-7 cells was lower than that of the control tumor cells. Moreover, the expression of zinc finger E-box binding homeobox 1 (ZEB1) increased after SNHG3 overexpression and vice versa. Overexpression of ZEB1 triggered cellular migration and invasion behaviors. Analysis of the mechanism underlying these effects suggested that SNHG3 is an effective sink for miR-186-5p and modulates ZEB1 repression, conferring an additional level to its post-transcriptional regulation. In conclusion, SNHG3 promotes the migration and invasion of breast cancer cells through miR-186-5p/ZEB1 regulation and the induction of the epithelial to mesenchymal transition, indicating that SNHG3 is a potential treatment target for breast cancer.