RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment.
RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment.
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DOI：
10.1038/s41598-018-21065-x
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发表时间：
2018-02-08
影响因子：
4.6
通讯作者：
Li CY
中科院分区：
文献类型：
--
作者：
Lin KH;Huang MY;Cheng WC;Wang SC;Fang SH;Tu HP;Su CC;Hung YL;Liu PL;Chen CS;Wang YT;Li CY
紫草素是一种从紫草干根中分离得到的萘醌，紫草是一种中药草药。虽然一些研究表明紫草素在乳腺癌中具有抗肿瘤活性，但其作用机制尚不清楚。本研究通过RNA-seq转录组分析，探讨紫草素调控不同类型乳腺癌细胞生长的作用机制。紫草素对MCF-7、SKBR-3和MDA-MB-231细胞的IC50分别为10.3 μΜ、15.0 μΜ、15.0 μΜ。我们的研究结果还表明，紫草素在MDA-MB-231细胞中具有抑制细胞周期进程和诱导细胞凋亡的作用。通过RNA-seq转录组分析，我们发现在紫草素治疗下，38个常见基因在不同类型的乳腺癌细胞中显著表达。特别是，我们的研究结果表明，紫草素在RNA和蛋白水平上诱导双特异性磷酸酶(DUSP)-1和DUSP2的表达。此外，紫草素还抑制DUSP1和DUSP2的下游信号分子JNK和p38的磷酸化。因此，我们的研究结果表明，紫草素诱导DUSP1和DUSP2的表达，从而关闭JNK和p38 MAPK通路，导致乳腺癌细胞周期阻滞和凋亡。
Shikonin is a naphthoquinone isolated from the dried root of Lithospermum erythrorhizon, an herb used in Chinese medicine. Although several studies have indicated that shikonin exhibits antitumor activity in breast cancer, the mechanism of action remains unclear. In the present study, we performed transcriptome analysis using RNA-seq and explored the mechanism of action of shikonin in regulating the growth of different types of breast cancer cells. The IC50 of shikonin on MCF-7, SKBR-3 and MDA-MB-231 cells were 10.3 μΜ, 15.0 μΜ, 15.0 μΜ respectively. Our results also demonstrated that shikonin arrests the progression of cell cycle and induces apoptosis in MDA-MB-231 cells. Using RNA-seq transcriptome analysis, we found 38 common genes that significantly express in different types of breast cancer cells under shikonin treatment. In particular, our results indicated that shikonin induces the expression of dual specificity phosphatase (DUSP)-1 and DUSP2 in both RNA and protein levels. In addition, shikonin also inhibits the phosphorylation of JNK and p38, the downstream signaling molecules of DUSP1 and DUSP2. Therefore, our results suggest that shikonin induces the expression of DUSP1 and DUSP2 which consequently switches off JNK and p38 MAPK pathways and causes cell cycle arrest and apoptosis in breast cancer cells.
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影响因子：
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通讯作者：
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