BHLHE41 suppresses MCF-7 cell invasion via MAPK/JNK pathway
BHLHE41 suppresses MCF-7 cell invasion via MAPK/JNK pathway
复制标题
BHLHE41 通过 MAPK/JNK 途径抑制 MCF-7 细胞侵袭
DOI：
10.1111/jcmm.15033
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发表时间：
2020-02-19
影响因子：
5.3
通讯作者：
Wang, Enhua
中科院分区：
文献类型：
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作者：
Zhang, Di;Zheng, Qin;Wang, Enhua
碱性螺旋-环-螺旋家族成员e41（BHLHE 41）的失调已被表征为几种癌症进展的标志物。本研究旨在探讨BHLHE 41调控乳腺癌细胞侵袭的机制。BHLHE 41抑制MCF-7和MDA-MB-231细胞的肿瘤侵袭，而BHLHE 41的沉默促进MCF-7和MDA-MB-231细胞的肿瘤侵袭。同时，BHLHE 41下调SNAI 1、SNAI 2、Vim和CDH 2的转录和翻译，上调CLDN 1、CLDN 4和CDH 1的转录和翻译。报告基因检测结果表明，BHLHE 41基因沉默后，MCF-7细胞中MAPK/JNK信号通路和MDA-MB-231细胞中缺氧信号通路明显激活。此外，BHLHE 41的沉默通过上调磷酸化JNK激活MAPK/JNK信号通路，并且不能影响MCF-7细胞中HIF-1 α的表达。用特异性抑制剂SP 600125阻断MAPK/JNK信号通路后，BHLHE 41的沉默不能促进肿瘤细胞的侵袭。这些结果表明BHLHE 41主要通过激活MAPK/JNK信号通路促进MCF-7细胞的侵袭。总之，尽管BHLHE 41抑制MCF-7和MDA-MB-231细胞系中的肿瘤侵袭，但具体的调节机制可能不同。
Deregulation of the basic helix-loop-helix family member e41 (BHLHE41) has been characterized as a marker of progression of several cancers. In this study, we aimed to explore the mechanism by which BHLHE41 regulates the invasion of breast cancer cells. BHLHE41 suppresses, whereas the silencing of BHLHE41 promotes tumour invasion of both MCF-7 and MDA-MB-231 cells. Meanwhile, BHLHE41 down-regulated the transcription and translation of SNAI1, SNAI2, VIM and CDH2, and up-regulated those of CLDN1, CLDN4 and CDH1. Reporter assay indicated that silencing of BHLHE41 dramatically activated the MAPK/JNK signalling pathway in MCF-7 cell line and the hypoxia signalling pathway in MDA-MB-231 cell line. Furthermore, silencing of BHLHE41 activated the MAPK/JNK signalling pathway by up-regulating phosphorylated JNK and failed to affect the expression of HIF-1 alpha in MCF-7 cells. After blocking the MAPK/JNK signalling pathway by specific inhibitor SP600125, silencing of BHLHE41 failed to promote tumour cell invasion. These results suggest that BHLHE41 facilitates MCF-7 cell invasion mainly via the activation of MAPK/JNK signalling pathway. In conclusion, although BHLHE41 suppresses tumour invasion in MCF-7 and MDA-MB-231 cell lines, the specific regulatory mechanisms may be different.