RESUMO
BACKGROUND: Kinesin superfamily (KIFs) has a long-reported significant influence on the initiation, development, and progress of breast cancer. However, the prognostic value of whole family members was poorly done. Our study intends to demonstrate the value of kinesin superfamily members as prognostic biomarkers as well as a therapeutic target of breast cancer. METHODS: Comprehensive bioinformatics analyses were done using data from TCGA, GEO, METABRIC, and GTEx. LASSO regression was done to select tumor-related members. Nomogram was constructed to predict the overall survival (OS) of breast cancer patients. Expression profiles were testified by quantitative RT-PCR and immunohistochemistry. Transcription factor, GO and KEGG enrichments were done to explore regulatory mechanism and functions. RESULTS: A total of 20 differentially expressed KIFs were identified between breast cancer and normal tissue with 4 (KIF17, KIF26A, KIF7, KIFC3) downregulated and 16 (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF20B, KIF22, KIF23, KIF24, KIF26B, KIF2C, KIF3B, KIF4A, KIFC1) overexpressed. Among which, 11 overexpressed KIFs (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIF4A, KIFC1) significantly correlated with worse OS, relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of breast cancer. A 6-KIFs-based risk score (KIF10, KIF15, KIF18A, KIF18B, KIF20A, KIF4A) was generated by LASSO regression with a nomogram validated an accurate predictive efficacy. Both mRNA and protein expression of KIFs are experimentally demonstrated upregulated in breast cancer patients. Msh Homeobox 1 (MSX1) was identified as transcription factors of KIFs in breast cancer. GO and KEGG enrichments revealed functions and pathways affected in breast cancer. CONCLUSION: Overexpression of tumor-related KIFs correlate with worse outcomes of breast cancer patients and can work as potential prognostic biomarkers.
RESUMO
BACKGROUND: Sustaining proliferation is the most fundamental step for breast cancer tumor genesis. Accelerated proliferation is usually linked to the uncontrolled cell cycle. However, the internal and external factors linked to the activation of breast cancer cell cycle are still to be investigated. METHODS: quantitative PCR (qPCR) and Western blotting assay were used to detect the expression of potassium channel tetramerization domain containing 12 (KCTD12) in breast cancer. MTT and colony formation assays were performed to evaluate the effect of KCTD12 on cell proliferation of breast cancer. Anchorage-independent growth assay was used to examine the in vitro tumorigenesis of breast cancer cells. Flow cytometry assay, qPCR, and Western blotting were used to investigate the detailed mechanisms of KCTD12 on breast cancer progression. RESULTS: Herein, the result showed that the level of KCTD12 is significantly decreased in breast cancer tissues and cells, and lower level of KCTD12 predicts poorer survival for patients with breast cancer. Further cell function tests illustrated that downregulation of KCTD12 significantly promotes cell proliferation and in vitro tumor genesis. Besides, molecular biologic experiments showed that downregulation of KCTD12 can enhance the G1/S transition through activating the AKT/FOXO1 signaling. CONCLUSION: Our study inferred that downregulation of KCTD12 can be a novel factor for poor prognosis in breast cancer.