This article is the original of the Translational Medicine Network, **Please indicate the source
Author: Sophia
Reading guide:Aurora-A kinase-interacting protein 1 (Aurkaip1) has been shown to play a mediating role in cancer by acting as a negative regulator of Aurora-A kinase. However, it is unclear whether and how aurkaip1 itself will be directly involved in the regulation of malignancies.
On December 1, researchers from Sun Yat-sen University and researchers from the First People's Hospital of Changde City, Hunan Province jointly published a study entitled "Aurkaip1 Actuates Tumor Progression Through Stabilizing DDX5 in Triple Negative Breast Cancer" in the journal Cell Death & DiseaseOur study mainly revealed the molecular mechanism by which the Aurkaip1 DDX5-Catenin axis regulates TNBC progression, suggesting that AurkaiP1 may serve as a target as well as a prognostic TNBC-specific biomarker.
Background:
There is no doubt that breast cancer remains the leading cause of cancer burden among women worldwide. Approximately 10% to 20% of breast cancers deficient in estrogen, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are classified as triple negative breast cancer (TNBC) and are invariably present to patients with TNBC** Challenge. More unfortunately, TNBC exhibits aggressive clinical behavior, which directly leads to a shorter survival time for this subset of breast cancer patients. ThereforeThere is still a need to explore potential specific targets for TNBC as a basis for future **.
Aurkaip1 (Aurora-A kinase-interacting protein 1) is an Aurora-A kinase-interacting protein involved in two degradation pathways of Aurora-A, including the proteasome-dependent pathway and the UB independent pathway. Ectopic expression of aurkaip1 leads to downregulation of aurora-a protein levels, and therefore, aurkaip1 can be considered as a cancer suppressor involved in the aurora-a pathway. Interestingly, elevated expression of aurkaip1 of the aurora kinase was also observed in several types of human cancer cells from breast, pancreatic, and bladder cancers. In addition to these conflicting findings, an even more surprising finding is that cells overexpressing Aurkaip1 can still survive and proliferate, even though AurkaOp1-negatively regulated Aurora-A kinase plays an important role in tumorigenesis. Elucidating the exact role and specific mechanism of aurkaip1 in human cancer will be full of implications.
Research Progress
Using QRT-PCR and Western blotting, we measured the mRNA and protein levels of AurkaiP1 in different cell lines, which showed that Aurkaip1 expression was significantly higher in TNBC cells compared to the normal mammary cell line MCF 10A (Figure 2A). To determine the biological effect of Aurkaip1 on TNBC, we first knocked down or overexpressed Aurkaip1 in MDA-MB-231 and BT 549 cell lines (Figure 2B). CCK8 proliferation assays (Fig. 2D) and clone formation assays (Fig. 2C) showed that siRNA-based Aurkaip1 knockdown greatly inhibited the proliferation ability of TNBC cells, while overexpression of AurkaiP1 completely enhanced the proliferation ability of TNBC cells. Importantly, these in vitro expectations are further confirmed by in vivo xenograft experiments (Figure 2E). Then, we performed transwell (Figure 3A, B)) and wound healing assays (Figure 3C) to assess whether AurkaiP1 affected TNBC cell migration. The results showed that silencing aurkaip1 significantly reduced cell migration ability, while overexpression of aurkaip1 showed the opposite effect. In summary, aurkaip1 inactivation impairs TNBC cell proliferation and migration in vitro and in vivo.
Aurkaip1 promotes cell proliferation and migration in triple-negative breast cancer (TNBC).
Contribution of aurkaip1 to TNBC cell migration.
Conclusions of the study
In conclusion, we mainly demonstrate that aurkaip1 is upregulated and associated with a poor prognosis in TNBC. AurkaiP1 can directly interact with DDX5 protein and stabilize DDX5 protein, increasing its expression and -catenin activity. Tumor growth can be slowed with siRNA**aurkaip1, which predicts that aurkaip1 is essential for tumorigenesis and aggressiveness of TNBC. Due to the limitations of the specimen, the association of aurkaip1 with DDX5 or -catenin amplification levels needs to be further studied, and more cases of TNBC need further study. Now that aurkaip1 can play a non-negligible role in TNBC, its additional protein chaperone and the underlying mechanisms of human cancer deserve in-depth study.
References: Note: This article aims to introduce the progress of medical research and cannot be used as a reference for ** scheme. If you need health guidance, please visit a regular hospital.
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