Zhang Chen, Xu Bingfei, Lu Shi, Zhao Ying, Liu Pian
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,, People's Republic of China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Mol Cancer. 2017 May 11;16(1):90. doi: 10.1186/s12943-017-0656-1.
Hematological and neurological expressed 1 (HN1) is upregulated in many tumors, but the role of HN1 in breast cancer progression and its regulatory mechanism have not been well understood.
To study the role of HN1 in the initiation and progression of breast cancer, we examined HN1 levels in breast cancer cells and tissues and analyzed the relationship between HN1 levels and patient survival. We used mammosphere formation assay, side population analysis, wound healing assay, transwell assay, soft agar formation assay, and xenografted tumor model to determine the effect of HN1 on the expansion of breast cancer stem cells, and the migration, invasion and tumorigenesis of breast cancer. To determine whether HN1 regulates MYC, we used quantitative real-time PCR and Western blot analysis to assess the expression of MYC and their targeted genes to determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1 overexpression.
In this study, we found that HN1 was upregulated in breast cancer tissues. Patients with high levels of HN1 expression had significantly shorter survival than those with low HN1 expression. In breast cancer cell line, ectopic overexpression of HN1 not only promoted the expansion of breast cancer stem cells, but also promoted cell migration, invasion, and tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there was a positive correlation between MYC (also known as c-MYC) level and HN1 level, mechanism analysis suggested HN1 promoted the expression of MYC and its targeted genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the effect of HN1 overexpression in breast cancer cell lines.
Taken together, these data reveal that HN1 promotes the progression of breast cancer by upregulating MYC expression, and might be a therapeutic target for breast cancer.
血液学和神经学表达1（HN1）在许多肿瘤中上调，但其在乳腺癌进展中的作用及其调控机制尚未完全明确。
为研究HN1在乳腺癌发生和进展中的作用，我们检测了乳腺癌细胞和组织中的HN1水平，并分析了HN1水平与患者生存之间的关系。我们使用乳腺球形成试验、侧群分析、伤口愈合试验、Transwell试验、软琼脂形成试验和异种移植肿瘤模型来确定HN1对乳腺癌干细胞扩增、乳腺癌迁移、侵袭和肿瘤发生的影响。为确定HN1是否调节MYC，我们使用定量实时PCR和蛋白质免疫印迹分析来评估MYC及其靶向基因的表达，以确定在HN1过表达的乳腺癌细胞中敲低MYC所导致的表型。
在本研究中，我们发现HN1在乳腺癌组织中上调。HN1高表达患者的生存期明显短于HN1低表达患者。在乳腺癌细胞系中，HN1的异位过表达不仅促进了乳腺癌干细胞的扩增，还促进了细胞迁移、侵袭和肿瘤发生，而敲低HN1则降低了这些作用。此外，MYC（也称为c-MYC）水平与HN1水平呈正相关，机制分析表明HN1促进了MYC及其靶向基因如CDK4、CCND1、p21、CAV1和SFRP1的表达。MYC的下调消除了HN1过表达在乳腺癌细胞系中的作用。
综上所述，这些数据表明HN1通过上调MYC表达促进乳腺癌进展，可能是乳腺癌的一个治疗靶点。
