Abstract
Kinesin family member 11 (KIF11) is a plus end‐directed kinesin indispensable for the formation of the bipolar spindle in metaphase, where it objects to the action of minus end‐directed molecular motors. Here, we hypothesize that KIF11 might be a therapeutic target of breast cancer and regulated by miR‐30a. Cell Counting Kit 8 assays were used to investigate cell proliferation. Invasion assays were used to survey the motility of cells. Kaplan‐Meier and Cox proportional analyses were employed for this outcome study. The prognostic significance and performance of KIF11 were validated on 17 worldwide independent microarray datasets and two The Cancer Genome Atlas‐Breast Invasive Carcinoma sets. microRNA was predicted targeting KIF11 through sequence alignment in microRNA.org and confirmed by coexpression analysis in human breast cancer samples. Dual‐luciferase reporter assays were employed to validate the interaction between miR‐30a and KIF11 further. Higher KIF11 mRNA levels and lower miR‐30a were significantly associated with poor survival of breast cancer patients. Inhibition of KIF11 by small‐hairpin RNA significantly reduced the proliferation and invasion capabilities of the breast cancer cells. Meanwhile, downregulation of KIF11 could enhance the cytotoxicity of adriamycin in breast cancer cell lines MCF‐7 and MDA‐MB‐231. A population study also validated that chemotherapy and radiotherapy significantly improved survival in early‐stage breast cancer patients with low KIF11 expression levels. Further bioinformatics analysis demonstrated that miR‐30a could interact with KIF11 and validated by dual‐luciferase reporter assays. Therefore, KIF11 is a potential therapeutic target of breast cancer. miR‐30a could specifically interact with KIF11 and suppress its expression in breast cancer.
Highlights
Breast cancer is one kind of the most common malignant cancers among females in the world, with approximately 1 000 000 new cases each year.[1,2] It is the second‐leading cause of death among women, accounts for 15% of all cancer deaths.[3]
There are a variety of subtypes with different biological behaviors and clinicopathologic features that can result in obviously different prognoses, which can be divided into four major molecular subtypes: luminal A (LumA), luminal B (LumB), triple‐negative/ basal‐like, and human epidermal growth factor receptor 2 (HER2) type.[4,5,6,7,8]
Our population study demonstrated that chemotherapy significantly improved the overall survival (OS) of stage II breast cancer patients with Kinesin family member 11 (KIF11)‐low expression in NKI dataset rather than with the KIF11‐high expression (Figure 4A)
Summary
Breast cancer is one kind of the most common malignant cancers among females in the world, with approximately 1 000 000 new cases each year.[1,2] It is the second‐leading cause of death among women, accounts for 15% of all cancer deaths.[3]. The protein of the kinesin family could function as molecular nanomotors It converts the free energy of nucleotide hydrolysis in coordinating the mechanical movement of microtubules.[9,10] As a member of the kinesin family, KIF11 is a microtubule‐dependent motor protein encoded by the KIF11 gene located at 10q24.1, with a primary function in mitotic spindle formation.[11] KIF11 is still an essential element for maintaining proper spindle dynamics and preserving spindle bipolarity in cell division. It has a catalytic motor/ATPase domain that mediates its interaction with ATP and microtubules. We investigated the role of KIF11 in the tumorigenesis and treatment of breast cancer and the possible role of miR‐30a in the regulation of KIF11 in this process
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