mRNA Expression of CDK2AP1 in Human Breast Cancer: Correlation with Clinical and Pathological Parameters

Abstract

Background: Cyclin-dependent kinase 2associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. Our objective was to determine if CDK2AP1 mRNA expression levels were consistent with tumour-suppressive functions in breast cancer. Materials and Methods: A total of 134 samples were analysed. CDK2AP1 mRNA levels were measured using quantitative polymerase chain reaction (RT-PCR) and normalised against glyceraldehyde 3-phosphate dehydrogenase mRNA. Levels in breast cancer and adjacent non-cancerous breast tissue were analysed against pathological and clinical parameters (TNM staging, survival over a 10-year follow-up period). Results: Normalised CDK2AP1 expression was 38-fold higher in adjacent noncancerous breast tissue than in breast cancer. CDK2AP1 expression in disease-free patients at 10 years was more than threefold that of patients who died of breast cancer. However, neither of these differences in expression levels reached statistical significance. CDK2AP1 mRNA levels were higher in TNM1 compared to TNM3 (p=0.016) and with TNM4 (p=0.016). There were no significant associations between CDK2AP1 expression and estrogen receptor status, tumour grade and tumour type. There was no significant difference in overall survival between patients with high and those with low CDK2AP1 mRNA levels after a median follow-up of 10 years (Kaplan-Meier analysis, p=0.872). Conclusion: To our knowledge, this is the first study in the literature to examine the mRNA expression of CDK2AP1 in human breast cancer over a long-term follow-up period. A compelling relationship exists between high CDK2AP1 mRNA expression and lower TNM classification of breast cancer, which is consistent with CDK2AP1 having a tumoursuppressive function. Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is hypothesised to be a tumour suppressor which works through the mediation of several other genes and proteins. First discovered in 1995 as 'deleted in oral cancer-1' (DOC1) gene (1), investigators have since found evidence for its growth-/tumour-suppressive action and confirmed it to be likely implicated in the development of many cancer types (2, 3). CDK2AP1 and its associated homolog CDK2AP2 likely work together to effectively suppress cell growth due to their probable structural and functional relation (4); CDK2AP2 is a known tumour suppressor (5) which we previously investigated and provided evidence for its tumour-suppressive function in human breast cancer. The interaction between the two was recorded by using CDK2AP1 as 'bait' in liver cDNA screening and was verified both in vitro and in cells (6). Multiple investigations have been conducted regarding the relationship between different micro-RNAs (miRs) and CDK2AP1. Using cells taken from the tumour-free surgical margins of 18 patients with head and neck squamous cell carcinomas, miR-21 was found to be inversely correlated with CDK2AP1 a...

[Retracted] LINC00518 Promotes Cell Malignant Behaviors via Influencing EIF4A3‐Mediated mRNA Stability of MITF in Melanoma

“…For instance, Smad4 mRNA suppresses cell metastasis in prostate cancer [ 31 ]. CDK2AP1 mRNA acts as an anticancer gene in the progression of human breast cancer [ 32 ]. The mRNA expression of MITF has been detected to be upregulated in melanoma [ 33 , 34 ].…”

Construction of the panoptosis-related gene model and characterization of tumor microenvironment infiltration in hepatocellular carcinoma

“…as a subunit of mitochondria, DAP3 is involved in the process of detachment from extracellular matrix-induced anoikis-induced apoptosis [ 33 ] and mediates IFN-induced apoptosis (interferon-γ), tumor necrosis factor receptor (TNF-α), Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) to induce apoptosis [ 24 ]. Meanwhile, DAP3 is at the location of several important cellular pathways in tumorigenesis and has been shown to be expressed at elevated levels in aggressive glioblastoma cells and glioma cell lines with an induced migration phenotype [ 34 ]; survival analysis by Gera et al [ 35 ] in a clinical study of a cohort of 127 breast cancer patients showed higher survival rates in the highly transcribed group. Galactose lectin-3 (LGALS3, also known as galectin-3), a member of the galectin protein family, is one of the most widely studied galactose lectins in cancer and is involved in a variety of cellular activities including apoptosis, cell migration, proliferation, and angiogenesis [ 36 – 38 ].…”

The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer

“…More interestingly, this significance was observed with PTEN and TP53 mutated samples. In breast cancer, Gera et al [ 15 ] reports that they found 39-fold increase of normalized mRNA expression of CDK2AP1 in noncancerous adjacent tissues [ 15 ]. Moreover, Xu et al [ 18 ] studied CDK2AP1 overexpression association with tumorigenesis in glioma in vitro and in vivo and found that, CDK2AP1 knockdown inhibits cells proliferation, and colony formation.…”

“…Varying levels of CDK2AP1 have been observed in tumors and adjacent non-cancerous normal tissues. Decreased expression has also been found in cancers such as breast [ 15 ], oral squamous cell carcinoma [ 16 ] and lung cancer [ 17 ]. On the contrary, a few studies reported high CDK2AP1 mRNA levels associate with tumorigenesis.…”

“…[ 18 ]. Furthermore, Gera et al [ 15 ] found 39-fold increased expression of CDK2AP1 in adjacent non-cancerous normal tissues when compared to breast tumors.…”