HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity

Abstract

BackgroundHematological 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.MethodsTo 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.ResultsIn 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.ConclusionTaken 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0656-1) contains supplementary material, which is available to authorized users.

Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met

“…Accordingly, our western blot results showed that HN1 knockdown reduced the expression of cyclin D1 and CDK4, them usually form a G1 phase cyclin‐CDK complex required for S phase entry; while up‐regulated the cell cycle inhibitor p21 WAF1/Cip1 . In breast cancer cells MCF‐7 and T47D, HN1 executed the same regulatory function on the expression of CDK4, cyclin D1, and p21; however, there is a contrary observation in PC‐3 prostate cancer cell that knockdown of HN1 resulted in nuclear accumulation of cyclin D1 …”

“…However, the cellular functions of HN1 are not fully understood yet. HN1 has been demonstrated to promote the progression of some types of cancer through different mechanisms, but its role in HCC is still unknown.…”

“…Hematological and neurological expressed 1 (HN1) gene, also called Jupiter microtubule associated homolog 1 (JPT1), encodes a small 16.5 kDa protein . Some evidences have demonstrated that HN1 is up‐regulated in certain cancers and control their progression, such as breast cancer, gliomas, melanoma, ovarian cancer, and prostate cancer . In terms of mechanism, it is reported that HN1 promotes the progression of breast cancer by up‐regulating MYC expression .…”

“…Some evidences have demonstrated that HN1 is up‐regulated in certain cancers and control their progression, such as breast cancer, gliomas, melanoma, ovarian cancer, and prostate cancer . In terms of mechanism, it is reported that HN1 promotes the progression of breast cancer by up‐regulating MYC expression . miR‐132 was reported to inhibit cell proliferation, invasion, migration and metastasis of breast cancer by targeting HN1 .…”

“…7 In terms of mechanism, it is reported that HN1 promotes the progression of breast cancer by up-regulating MYC expression. 3 miR-132 was reported to inhibit cell proliferation, invasion, migration and metastasis of breast cancer by targeting HN1. 8 In prostate cancer, HN1 interacts with GSK3β/βcatenin destruction complex to promote β-catenin degradation and negatively influences the β-catenin/E-cadherin interaction, contributes to cell growth and migration.…”