A-kinase-interacting Protein 1 Research Articles

A Kinase Interacting Protein 1 regulates mitochondrial protein levels in energy metabolism and promotes mitochondrial turnover after exercise

A Kinase Interacting Protein 1 (AKIP1) is a signalling adaptor that promotes mitochondrial respiration and attenuates mitochondrial oxidative stress in cultured cardiomyocytes. We sought to determine whether AKIP1 influences mitochondrial function and the mitochondrial adaptation in response to exercise in vivo. We assessed mitochondrial respiratory capacity, as well as electron microscopy and mitochondrial targeted-proteomics in hearts from mice with cardiomyocyte-specific overexpression of AKIP1 (AKIP1-TG) and their wild type (WT) littermates. These parameters were also assessed after four weeks of voluntary wheel running. In contrast to our previous in vitro study, respiratory capacity measured as state 3 respiration on palmitoyl carnitine was significantly lower in AKIP1-TG compared to WT mice, whereas state 3 respiration on pyruvate remained unaltered. Similar findings were observed for maximal respiration, after addition of FCCP. Mitochondrial DNA damage and oxidative stress markers were not elevated in AKIP1-TG mice and gross mitochondrial morphology was similar. Mitochondrial targeted-proteomics did reveal reductions in mitochondrial proteins involved in energy metabolism. Exercise performance was comparable between genotypes, whereas exercise-induced cardiac hypertrophy was significantly increased in AKIP1-TG mice. After exercise, mitochondrial state 3 respiration on pyruvate substrates was significantly lower in AKIP1-TG compared with WT mice, while respiration on palmitoyl carnitine was not further decreased. This was associated with increased mitochondrial fission on electron microscopy, and the activation of pathways associated with mitochondrial fission and mitophagy. This study suggests that AKIP1 regulates the mitochondrial proteome involved in energy metabolism and promotes mitochondrial turnover after exercise. Future studies are required to unravel the mechanistic underpinnings and whether the mitochondrial changes are required for the AKIP1-induced physiological cardiac growth.

Prognostic Value of Immunohistochemical Expression of MTAP and AKIP1 in IDH1 Mutant Astrocytoma.

Definite treatment for glioma is not exist, and with increased drug resistance, more effort should be paid to identify new prognostic biomarkers and molecular targets for therapy for glioma patients. The current study aimed to evaluate the immunohistochemical (IHC) expression of MTAP and A-Kinase Interacting Protein 1 (AKIP1) in astrocytoma and to investigate their association with the clinicopathological characters of these cases. Totally 66 cases of astrocytoma patients involved in this study. Cases underwent tumor resection and tissue sections were stained with MTAP, AKIP1 and IDH1 by IHC and evaluated in different grades of astrocytoma and their association with survival and response to therapy was investigated. High AKIP1 expression was positively correlated with treatment resistance and progressive disease. Positive IDH and retained MTAP expressions had shown better treatment response rather than negative IDH and lost MTAP. High AKIP, negative IDH and loss of MTAP expressions were significantly associated with poor survival outcome. Irrespective to grade and IDH status, the loss of MTAP immunoreactivity and high AKIP1 expression are predictive factors in astrocytoma, and they may be used as a biomarker for guiding astrocytoma management and prognosis surveillance.

AKIP1 accelerates glioblastoma progression through stabilizing EGFR expression.

A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients' worse prognosis. Several studies have established AKIP1's malignant functions in tumor metastasis, angiogenesis, and chemoradiotherapy resistance. However, the mechanism of AKIP1 involved in accelerating glioblastoma (GBM) progression remains unknown. Here, we showed that the expression of AKIP1 was positively correlated with the glioma pathological grades. Down-regulating AKIP1 greatly impaired the proliferation, colony formation, and tumorigenicity of GBM cells. In terms of the mechanism, AKIP1 cooperates with transcriptional factor Yin Yang 1 (YY1)-mediated Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) transcriptional activation, enhancing the stability of Epidermal Growth Factor Receptor (EGFR). YY1 was identified as a potential transcriptional factor of HSP90AA1 and directly interacts with AKIP1. The overexpression of HSP90α significantly reversed AKIP1 depletion incurred EGFR instability and the blocked cell proliferation. Moreover, we further investigated the interacted pattern between EGFR and HSP90α. These findings established that AKIP1 acted as a critical oncogenic factor in GBM and uncovered a novel regulatory mechanism in EGFR aberrant expression.

A Kinase Interacting Protein 1 (AKIP1) promotes cardiomyocyte elongation and physiological cardiac remodelling

A Kinase Interacting Protein 1 (AKIP1) is a signalling adaptor that promotes physiological hypertrophy in vitro. The purpose of this study is to determine if AKIP1 promotes physiological cardiomyocyte hypertrophy in vivo. Therefore, adult male mice with cardiomyocyte-specific overexpression of AKIP1 (AKIP1-TG) and wild type (WT) littermates were caged individually for four weeks in the presence or absence of a running wheel. Exercise performance, heart weight to tibia length (HW/TL), MRI, histology, and left ventricular (LV) molecular markers were evaluated. While exercise parameters were comparable between genotypes, exercise-induced cardiac hypertrophy was augmented in AKIP1-TG vs. WT mice as evidenced by an increase in HW/TL by weighing scale and in LV mass on MRI. AKIP1-induced hypertrophy was predominantly determined by an increase in cardiomyocyte length, which was associated with reductions in p90 ribosomal S6 kinase 3 (RSK3), increments of phosphatase 2A catalytic subunit (PP2Ac) and dephosphorylation of serum response factor (SRF). With electron microscopy, we detected clusters of AKIP1 protein in the cardiomyocyte nucleus, which can potentially influence signalosome formation and predispose a switch in transcription upon exercise. Mechanistically, AKIP1 promoted exercise-induced activation of protein kinase B (Akt), downregulation of CCAAT Enhancer Binding Protein Beta (C/EBPβ) and de-repression of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4 (CITED4). Concludingly, we identified AKIP1 as a novel regulator of cardiomyocyte elongation and physiological cardiac remodelling with activation of the RSK3-PP2Ac-SRF and Akt-C/EBPβ-CITED4 pathway. These findings suggest that AKIP1 may serve as a nodal point for physiological reprogramming of cardiac remodelling.

A-kinase interacting protein 1 regulates the cell proliferation, invasion, migration and angiogenesis of clear cell renal cell carcinoma cells and affects the ERK/c-Myc signaling pathway by binding to Rac1.

A-kinase interacting protein 1 (AKIP1) has previously been demonstrated to be overexpressed in clear cell renal cell carcinoma (ccRCC) tissues and is associated with patient prognosis. The aim of the present study was to explore whether AKIP1 can affect the proliferation, invasion, migration and angiogenesis of ccRCC cells via its interaction with Rac1. Furthermore, the influence of AKIP1 and therefore Rac1 on the expression of the downstream ERK/cellular (c)-Myc signaling pathway was explored. The interaction between AKIP1 and Rac1 was determined using co-immunoprecipitation. The mRNA and protein expression levels of AKIP1 and Rac1 in normal renal epithelial cell lines and ccRCC cell lines were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. The transfection efficiency of small interfering RNA-AKIP1 and the Rac1 overexpression vector were also confirmed using RT-qPCR and western blotting. The viability, proliferation, invasion and migration of ccRCC cells following transfection were analyzed using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, Transwell and wound healing assays, respectively. The tube formation ability of HUVECs was assessed using the tube formation assay. The protein expression levels of proliferation, invasion, migration and tube-formation-associated proteins as well as proteins associated with the ERK/c-Myc signaling pathway, were detected via western blotting. The results demonstrated that AKIP1 expression levels were increased in ccRCC cell lines. AKIP1 knockdown inhibited the proliferation, invasion and migration of ccRCC cells and HUVEC tube-formation. In addition, AKIP1 was demonstrated to bind to Rac1 in ccRCC cells and AKIP1 downregulation inhibited Rac1 expression. Furthermore, Rac1 overexpression reversed the effects of AKIP1 knockdown on ccRCC cells. AKIP1 knockdown also suppressed the ERK/c-Myc signaling pathway, which was reversed by Rac1 overexpression. In conclusion, AKIP1 knockdown potentially suppressed the proliferation, invasion, migration and angiogenesis of ccRCC cells and inhibited the ERK/c-Myc signaling pathway by binding to Rac1.

Prognostic significance of A-kinase interacting protein 1 expression in various cancers: A meta-analysis based on the Chinese population.

Background:Cumulative evidence suggests that A-kinase interacting protein 1 (AKIP1) plays an important role in tumor progression. However, the prognostic value of AKIP1 expression in various cancers remains unclear. Here, we conducted a meta-analysis to evaluate the prognostic value of AKIP1 expression in patients with cancer.Methods:The PubMed, Web of Science, EMBASE, CNKI, and Wanfang databases were systematically searched to identify studies in which the effect of AKIP1 expression on prognosis (overall survival or disease-free survival) was investigated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the effect of AKIP1 expression on patient survival. Odds ratios (ORs) with 95% CIs were pooled to estimate the association between AKIP1 expression and clinicopathological characteristics of patients with cancer.Results:Nineteen eligible studies, encompassing 3979 patients, were included in the meta-analysis. AKIP1 expression was negatively associated with overall survival (HR = 1.86, 95% CI: 1.58–2.18, P < .001) and disease-free survival (HR = 1.69, 95% CI: 1.53–1.87, P < .001) in patients with cancer. Moreover, AKIP1 overexpression was positively correlated with adverse clinicopathological features, such as tumor size (OR = 2.22, 95% CI: 1.67–2.94, P < .001), clinical stage (OR = 2.05, 95% CI: 1.45–2.90, P < .001), depth of tumor invasion (OR = 2.98, 95% CI: 2.21–4.02, P < .001), and degree of lymph node metastasis (OR = 2.12, 95% CI: 1.75–2.57, P < .001).Conclusions:High AKIP1 expression is an unfavorable prognostic biomarker and may serve as a potential therapeutic target in patients with cancer.

Elevated AKIP1 expression is associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma.

A-kinase-interacting protein 1 (AKIP1), as a recently discovered oncoprotein, promotes cell malignant behaviors in gynecological malignancies. To the best of our knowledge, no study reports its clinical value in patients with endometrial carcinoma. The present study aimed to explore the association between AKIP1 expression and clinical features and survival in patients with endometrial carcinoma, and to assess the effect of AKIP1 knockdown on the regulation of chemosensitivity in vitro. The tumor and adjacent tissue specimens from 101 patients with endometrial carcinoma were retrieved for AKIP1 protein expression analysis using an immunohistochemistry (IHC) assay. Meanwhile, specimens from 54 patients with endometrial carcinoma were analyzed for AKIP1 mRNA expression using reverse transcription-quantitative PCR. Furthermore, an in vitro experiment was conducted in the Ishikawa cell line to determine the effect of AKIP1 modification on the chemosensitivity of cisplatin and paclitaxel. AKIP1 IHC score (P<0.001) and mRNA expression levels (P<0.001) were increased in tumor tissues compared with those in adjacent tissues. Moreover, increased AKIP1 IHC score was associated with lymphovascular invasion (P=0.007), advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.002) and shorter overall survival (OS) time (P=0.035) in the patients with endometrial carcinoma. Meanwhile, upregulated AKIP1 mRNA expression levels were associated with lymphovascular invasion (P=0.020) and advanced FIGO stage (P=0.027) in the patients with endometrial carcinoma. Multivariate Cox regression showed that tumor AKIP1 protein expression (high vs. low) independently predicted a shorter OS time (P=0.036). Silencing of AKIP1 decreased Ishikawa cell viability when treated with 5, 10, 20 and 40 µM cisplatin (all P<0.05) and decreased the half maximal inhibitory concentration value of cisplatin (P=0.003), whereas its effect on paclitaxel chemosensitivity was less obvious. Overall, elevated AKIP1 expression was associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma.

Silencing of AKIP1 Suppresses the Proliferation, Migration, and Epithelial-Mesenchymal Transition Process of Glioma Cells by Upregulating DLG2.

Gliomas, the most prevalent brain tumors, account for nearly one-third of the all brain and central nervous system (CNS) tumors diagnosed in the USA. The purpose of this study was to discuss the important role of A kinase-interacting protein 1 (AKIP1) in glioma and reveal the potential mechanism. After prediction by CCLE, the expression of AKIP1 was determined by qRT-PCR and western blot. The impacts of AKIP1 knockdown on the proliferation, migration, and invasion were then measured by MTT, colony formation assay, wound healing, and transwell assays. Western blot was used to assess the protein levels of migration and epithelial-mesenchymal transition- (EMT-) related factors. Subsequently, the expression of Disks Large Homolog 2 (DLG2) was predicted by bioinformatics analyses, and the interaction between AKIP1 and DLG2 was confirmed by IP assay, qRT-PCR, and western blot. Finally, DLG2 was further downregulated in glioma cells to detect the association between AKIP1 and DLG2 in the cellular functions of glioma. It was demonstrated that AKIP1 exhibited a high level in glioma cells, and interference of AKIP1 led to reductions in the proliferation, migration, invasion, and EMT of glioma cells. DLG2, which was lowly expressed in glioma cells, demonstrated a negative link to AKIP2. Inhibition of both AKIP2 and DLG2 counteracted the inhibited cellular behaviors on account of AKIP1 interference. To be concluded, this study presented evidence that AKIP1 silencing suppressed the progression of glioma via targeting DLG2, which could provide novel insights to impede the development of glioma.

Perfluorooctane sulfonate (PFOS) triggers migration and invasion of esophageal squamous cell carcinoma cells via regulation of Zeb1

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly cancers worldwide, especially in Eastern Asia. As a potential endocrine-disrupting chemical (EDC), perfluorooctane sulfonate (PFOS) can mimic estrogen, disturb the estrogen signals, and then cause various diseases. Although ESCC can be directly exposed to PFOS during food digestion, the effects and mechanisms of PFOS on the development of ESCC are still not well illustrated. This study showed that PFOS can promote the migration and invasion of ESCC cells. Further, PFOS treatment can increase the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while decreasing the expression of E-Cadherin (E-Cad). Zeb1, an important transcription factor for cell motility, was essential for PFOS induced migration and invasion of ESCC cells. PFOS can increase the expression of Zeb1 via upregulation of its transcription and proteins stability. A-kinase interacting protein 1 (AKIP1) and ataxia-telangiectasia mutated (ATM) were responsible for PFOS induced transcription and proteins stability of Zeb1 in ESCC cells, respectively. Collectively, our data indicated that environmental exposure and body accumulation of PFOS might be an important risk factor for ESCC progression.

Upregulation of a kinase interacting protein 1 in tongue squamous cell carcinoma correlates with lymph node metastasis and poor overall survival.

A kinase interacting protein 1 (AKIP1) is upregulated in cancer cells/tissues and associated with deteriorative tumor features, while it has not been investigated in tongue squamous cell carcinoma (TSCC). The goal of this study was to measure AKIP1 expression and analyze its correlation with clinical feature and prognosis in TSCC patients.We retrospectively reviewed 194 TSCC patients, whose formalin fixed paraffin-embedded (FFPE) tumor tissue specimens and paired adjacent tissue specimens were accessible for AKIP1 detection by immunohistochemistry (IHC). Whereas only 107 patients whose fresh-frozen tumor tissue and paired fresh-frozen adjacent tissue that were still available in storage were included for AKIP1 mRNA detection by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).AKIP1 expression (both the protein detected by IHC and mRNA detected by RT-qPCR) was higher in TSCC tissue than that in adjacent tissue. In addition, both tumor AKIP1 mRNA and protein expressions were correlated with advanced N stage and TNM stage, while they were not correlated with other clinical features in TSCC patients. As for survival, there was a correlation of AKIP1 mRNA with poor overall survival (OS), while the correlation of AKIP1 protein expression with OS was of limited statistical significance.There is an upregulation of AKIP1 in TSCC and it correlates with lymph node metastasis as well as unfavorable prognosis in TSCC patients.

A kinase-interacting protein 1 may serve as a potential biomarker for deteriorative tumor features and poor prognosis in gastric cancer patients.

ObjectiveThis study aimed to explore the association of A kinase‐interacting protein 1 (AKIP1) expression with clinicopathological characteristics and prognosis in gastric cancer patients.MethodsData of 260 gastric cancer patients were retrospectively reviewed. AKIP1 expression in tumor tissue and non‐cancerous tissue specimens was detected by immunohistochemistry and semi‐quantitatively scored according to the staining intensity and density. Moreover, the clinicopathological features were retrieved, and disease‐free survival (DFS) and overall survival (OS) were calculated.ResultsA kinase‐interacting protein 1 expression was increased in tumor tissues compared with non‐cancerous tissues (P < .001). In terms of tumor features, tumor AKIP1 high expression correlated with elevated T stage (P < .001) and raised TNM stage (P = .042), while did not correlate with pathological grade (P > .999), tumor size (P = .060), N stage (P = .180), or tumor location (P > .999). Meanwhile, tumor AKIP1 was not associated with the non‐tumor features either. Kaplan‐Meier curves disclosed that AKIP1 high expression patients had shorter DFS (P = .004) and OS (P = .043) compared with AKIP1 low expression patients. Univariate Cox's regression showed that AKIP1 high expression correlated with shorter DFS (P = .005, hazard ratio [HR] = 1.635) and OS (P = .046, HR = 1.519), whereas multivariate Cox's regression displayed that AKIP1 did not independently predict worse DFS (P = .172, HR = 1.276) or shorter OS (P = .433, HR = 1.183).ConclusionA kinase‐interacting protein 1 may serve as a potential biomarker for deteriorative tumor features and poor prognosis in gastric cancer patients.

A-kinase interacting protein 1 as a potential biomarker of advanced tumor features and increased recurrence risk in papillary thyroid carcinoma patients.

BackgroundThis study aimed to detect the expression of A‐kinase interacting protein 1 (AKIP1) and explore its correlation with clinicopathological features and clinical outcomes in papillary thyroid carcinoma (PTC) patients.MethodsA total of 245 PTC patients treated by lobectomy or thyroidectomy were analyzed in this retrospective study. AKIP1 expression in tumor and adjacent tissue (from Specimen Room of our hospital) was detected by immunohistochemical (IHC) assay and then categorized as four grades: AKIP1 low (IHC score ≤3), high+ (IHC score 4‐6), high++ (IHC score 7‐9), and high+++ (IHC score 10‐12).ResultsA‐kinase interacting protein 1 low, high+, high++, and high+++ expression was 101 (41.2%), 101 (41.2%), 32 (13.1%), and 11 (4.5%) in tumor tissues, while was 173 (70.6%), 61 (24.9%), 9 (3.7%), and 2 (0.8%) in adjacent tissues. Further comparison analysis showed increased grade of AKIP1 expression in tumor tissues compared to adjacent tissue. Meanwhile, increased grade of tumor AKIP1 expression was correlated with larger tumor size, extrathyroidal invasion, increased pT stage, and higher pTNM stage. For prognosis, increased grade of tumor AKIP1 expression was correlated with shorter disease‐free survival (DFS), while was not correlated with overall survival (OS). Forward stepwise multivariate Cox's regression revealed that higher tumor AKIP1 was an independent factor predicting worse DFS, but not OS.ConclusionAKIP1 is upregulated in tumor tissue, and increased tumor AKIP1 expression correlates with advanced tumor features and increased recurrence risk in PTC patients, which suggest that AKIP1 severs as a potential marker for effective supervision of PTC progression.

A-kinase interacting protein 1 high expression correlates with advanced tumor stage and poor overall survival in surgical patients with clear cell renal cell carcinoma.

The present study aimed to detect the A-kinase interacting protein 1 (AKIP1) expression in clear cell renal cell carcinoma (ccRCC) tumor tissues and adjacent tissues, and further investigate the correlation of tumor AKIP1 expression with clinicopathological features and survival profile in ccRCC patients.Totally 210 ccRCC patients who underwent resection were retrospectively reviewed, and their tumor and adjacent tissue specimens were acquired for immunohistochemical detection of AKIP1 expression. The survival data of patients were collected for overall survival (OS) assessment.AKIP1 was upregulated in ccRCC tumor tissues compared with adjacent tissues (P < .001). Tumor AKIP1 expression was positively associated with T stage (P = .019), N stage (P = .032), and TNM stage (P = .005) in ccRCC patients. According to AKIP1 expression in tumor tissues, all patients were grouped as AKIP1 low and high expression (AKIP1 high expression were further divided into AKIP1 high+, high++, and high+++ expression). OS was the lowest in the patients with AKIP1 high+++ expression, followed by those with AKIP1 high++ expression and AKIP1 high+ expression, and then patients with AKIP1 low expression (P < .001). Furthermore, multivariate Cox regression exhibited tumor AKIP1 high expression (P = .017), age (>60 years) (P = .030), pathological grade (G2/G3 vs G1) (P = .037), and TNM stage (II/III vs I) (P < .001) were independent predictive factors for decreased OS in ccRCC patients.AKIP1 presents potency to be a novel biomarker for tumor progression and prognosis surveillance in ccRCC.

A-kinase-interacting protein 1 promotes EMT and metastasis via PI3K/Akt/IKKβ pathway in cervical cancer.

Overexpression of A‐kinase‐interacting protein 1 (AKIP1) has been reported in prostate and breast cancers. Nevertheless, the clinical potential of AKIP1 during the development of cervical cancer (CC) remains unclear. A series of experiments involving BdU, colony formation, wound healing and cell invasion assays were performed to determine cell proliferation, migration and invasion, respectively. Gene expression changes were validated by qRT‐PCR, Western blotting and immunocytochemistry. We found that AKIP1 expression is increased in CC cell lines and tissue specimens from CC patients. The elevated AKIP1 expression in primary tumours was related to lymph node metastasis in CC patients. In addition, we observed that overexpression of AKIP1 promotes CC cell proliferation. Enhanced expression of AKIP1 facilitated the migration and invasion of CC cells by inducing NF‐κB‐dependent epithelial‐mesenchymal transition (EMT). Moreover, mechanistic investigations revealed that AKIP1 induced nuclear translocation and phosphorylation of the p65 NF‐κB subunit through the PI3K/Akt/IKKβ pathway. Conversely, enhanced expression of phosphatase and tensin homologue (PTEN) inhibited this signalling pathway and restored an epithelial phenotype to CC cells in the presence of overexpressed AKIP1. Our results indicate that AKIP1 promotes the EMT and metastasis in CC by activating NF‐κB signalling through the PI3K/Akt/IKKβ pathway, suggesting that AKIP1 could be a pivotal regulator of an EMT axis in CC.Significance of the studyAKIP1 expression in the samples of CC patients and in in vitro tumour cell lines provides evidence that expression of AKIP1 in CC contributes to cancer progression. Our findings indicate that AKIP1 promotes the epithelial‐mesenchymal transition and metastasis in CC by activating NF‐κB signalling through the PI3K/Akt/IKKβ pathway, suggesting that AKIP1 is a pivotal regulator of an EMT axis in CC. AKIP1 could be implicated as a potential therapeutic target as well as a valuable biomarker for evaluating prognosis for patients with CC.

Identification of A‐kinase interacting protein 1 as a potential biomarker for risk and prognosis of acute myeloid leukemia

BackgroundThis study aimed to investigate the correlation of A‐kinase interacting protein 1 (AKIP1) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML).Methods291 de novo AML patients and 97 controls were consecutively recruited, and bone marrow samples were collected to detect AKIP1 expression using quantitative polymerase chain reaction prior to initial treatment. Treatment response, event‐free survival (EFS), and overall survival (OS) in AML patients were evaluated.ResultsA‐kinase interacting protein 1 expression was higher in AML patients than that in controls; meanwhile, receiver operating characteristic curve displayed that AKIP1 was able to distinguish AML patients from controls (area under the curve:0.772, 95%CI: 0.720‐0.823). Among AML patients, AKIP1 high expression was correlated with −7 or 7q−, monosomal karyotype, and worse risk stratification. Moreover, AKIP1 expression was negatively correlated with complete remission achievement, while no correlation of AKIP1 expression with hematopoietic stem cell transplantation achievement was observed. AKIP1 high expression was associated with shorter EFS and OS in total patients, and further subgroup analysis exhibited that AKIP1 high expression correlated with worse EFS and OS in intermediate‐risk and poor‐risk patients but not in better‐risk patients. Besides, subsequent analysis revealed that AKIP1 high expression was an independent factor predicting unfavorable EFS and OS.ConclusionA‐kinase interacting protein 1 has the potential to be a novel marker for assisting AML management.

A-kinase interacting protein 1, a potential biomarker associated with advanced tumor features and CXCL1/2 in prostate cancer.

This study aimed to investigate the correlation of A-kinase interacting protein 1 (AKIP1) with chemokine (C-X-C motif) ligand 1 (CXCL1) and CXCL2, as well as their associations with clinical characteristics and prognosis in prostate cancer patients. A total of 248 eligible prostate cancer patients who underwent surgery were consecutively recruited, and tumor tissues were collected during the surgery. AKIP1, CXCL1, and CXCL2 expression in tumor tissues were assessed by immunohistochemistry. Disease-free survival and overall survival were recorded, and the median follow-up time was 27 months. The proportion of patients with AKIP1, CXCL1, and CXCL2 high expression was 56.5%, 63.7%, and 56.9%, respectively. Additionally, AKIP1 expression positively correlated with CXCL1 expression (P<0.001) and CXCL2 expression (P<0.001), and CXCL1 expression was positively associated with CXCL2 expression (P<0.001). Furthermore, AKIP1 expression positively correlated with pathological T stage (P<0.001) and pathological N stage (P=0.003). CXCL1 expression was positively associated with pathological T stage (P<0.001) and pathological N stage (P<0.001) as well. However, the CXCL2 expression only positively correlated with pathological T stage (P=0.002). Also, AKIP1 high expression correlated with worse disease-free survival (P=0.049) and OS (P=0.013), and CXCL1 high expression was associated with unfavorable disease-free survival (P=0.023) but not overall survival (P=0.052). CXCL2 expression was not correlated with disease-free survival (P=0.083) or overall survival (P=0.065). Multivariate Cox's regression disclosed that AKIP1 high expression independently predicted worse overall survival (P=0.009). AKIP1 positively associates with CXCL1/2 and is a potential biomarker for disease monitoring as well as prognosis in prostate cancer.

A-kinase interacting protein 1 (AKIP1) associates with advanced overall disease condition, tumor properties, and unfavorable prognosis in hepatocellular carcinoma patients.

ObjectiveThe presented study aimed to investigate the association of A‐kinase interacting protein 1 (AKIP1) expression with tumor properties, liver functions, cancer markers, and overall survival (OS) of hepatocellular carcinoma (HCC) patients.MethodsA total of 432 HCC patients receiving surgery were retrospectively reviewed in our study. Clinical characteristics of patients were obtained. Tumor tissue specimens of all patients were collected, and AKIP1 expression was evaluated by immunohistochemistry (IHC) assay. OS was assessed, and the median follow‐up duration was 35.0 months. AKIP1 high expression was defined as total IHC score more than 3 and was further graded as AKIP1 high+ (IHC 4‐6), AKIP1 high++ (IHC 7‐9), and AKIP1 high+++ (IHC 10‐12).ResultsAbout 265 (61.3%) patients presented with AKIP1 low expression and 167 (38.7%) patients had AKIP1 high expression. AKIP1 high expression correlated with higher performance status score (P = .006), largest tumor size ≥5.0 cm (P < .001), Barcelona clinic liver cancer (BCLC) stage B (vs stage A; P = .024), increased alpha‐fetoprotein level (P = .036), and higher carbohydrate antigen 199 level (P < .001). AKIP1 high expression (P < .001) and increased AKIP1 expression grade (P < .001) both correlated with worse OS, and Cox's regression analyses revealed that AKIP1 high expression (P < .001) was an independent predictive factor for shorter OS. In subgroup analysis, AKIP1 high expression and more advanced AKIP1 expression grade associated with worse OS in both BCLC stage A subgroup patients (both P < .001) and BCLC stage B subgroup patients (both P < .001), respectively.ConclusionAKIP1 is a novel and promising biomarker for disease monitoring and prognosis in HCC patients.

Correlations of AKIP1, CXCL1 and CXCL2 expressions with clinicopathological features and survival profiles in cervical cancer patients.

BackgroundThis study aimed to evaluate the correlation of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL) 1 and CXCL2, and their associations with clinical characteristics and prognosis in cervical cancer patients.MethodsOne hundred and fifty early-stage cervical cancer patients treated with surgical resection were reviewed and tumor tissue samples were obtained. Expression of AKIP1, CXCL1 and CXCL2 was detected by immunohistochemistry (IHC). Data of tumor features were retrieved, and disease-free survival (DFS) as well as overall survival (OS) were calculated.ResultsAKIP1 expression was positively correlated with CXCL1 and CXCL2 expression in cervical cancer tissue (both P<0.001). AKIP1 expression was positively correlated with tumor size (P=0.040), lymph node (LYN) metastasis (P=0.034) and International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.021); CXCL1 expression was positively associated with tumor size (P=0.048); and CXCL2 expression was positively correlated with LYN metastasis (P=0.026). As for DFS and OS, AKIP1 high expression was correlated with worse DFS (P=0.016) and OS (P=0.007), CXCL1 high expression was associated with poor DFS (P=0.029) but not OS (P=0.118). No correlation of CXCL2 expression with DFS (P=0.141) or OS (P=0.125) was found.ConclusionsAKIP1 positively correlates with CXCL1/CXCL2, and associates with advanced tumor features as well as unfavorable survival profiles in cervical cancer patients.

A-kinase-interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles, and promotes cell proliferation but represses apoptosis in non-small-cell lung cancer.

BackgroundThis study aimed to explore the correlation of A‐kinase‐interacting protein 1 (AKIP1) expression with clinical characteristics as well as survival profiles in non‐small‐cell lung cancer (NSCLC) patients, and further investigate its underlying effect on regulating NSCLC cell functions.Methods319 NSCLC patients who underwent resection were consecutively reviewed, and AKIP1 expression (in 319 tumor tissues and 145 adjacent tissues) was determined by immunohistochemistry. Disease‐free survival (DFS) and overall survival (OS) were calculated. In vitro, control overexpression, AKIP1 overexpression, control shRNA and AKIP1 shRNA plasmids were transfected into A549 cells to evaluate the effect of AKIP1 on cell proliferation and apoptosis.ResultsA‐kinase‐interacting protein 1 expression was increased in tumor tissues compared to adjacent tissues, and it positively correlated with tumor size, lymph node metastasis and TNM stage in NSCLC patients. Kaplan‐Meier curves displayed that AKIP1 high expression correlated with worse DFS and OS, and multivariate Cox's regression revealed that it was an independent predictive factor for poor survival profiles. In vitro experiments displayed that AKIP1 expression was elevated in PC9 and A549 cells compared to normal lung epithelial cells; moreover, cell proliferation was increased by AKIP1 upregulation but reduced by AKIP1 downregulation, and cell apoptosis was decreased by AKIP1 upregulation but increased by AKIP downregulation in A549 cells. Interestingly, AKIP1 promoted fibronectin and zinc finger E‐box binding homeobox 1 expressions while reduced E‐cadherin expression in A549 cells.ConclusionA‐kinase‐interacting protein 1 overexpression correlates with deteriorative tumor features and worse survival profiles and promotes cell proliferation but represses apoptosis in NSCLC.

AKIP1 expression in tumor tissue as a new biomarker for disease monitoring and prognosis in non-small cell lung cancer: Results of a retrospective study.

BackgroundA‐kinase–interacting protein 1 (AKIP1) has been reported as an oncogenetic factor in multiple cancers; however, no study has reported its role in non‐small cell lung cancer (NSCLC) yet. This study aimed to evaluate the expression of AKIP1, and its correlation with tumor characteristics as well as prognosis in patients with NSCLC.MethodsFour hundred and ninety patients with NSCLC who underwent resection were reviewed, and baseline clinical data were collected. AKIP1 expression in tumor tissue/paired adjacent tissue was detected by immunohistochemistry. Disease‐free survival (DFS) and overall survival (OS) were calculated.ResultsA‐kinase–interacting protein 1 expression was elevated in tumor tissue compared with paired adjacent tissue (P < .001), and high AKIP1 tumor tissue expression was correlated with poor pathological differentiation (P < .001), tumor size >5 cm (P = .001), lymph node metastasis (P = .016), higher TNM stages (P < .001), and abnormal CEA level (>5 ng/mL) (P = .035). DFS was worse in patients with tumor tissue AKIP1 high expression compared with patients who had AKIP1 low expression in total patients (P < .001), TNM stage I (P < .001) and TNM stage III (P < .001) patients. And the OS was also decreased in patients with AKIP1 high expression in total patients (P < .001), TNM stage I patients (P = .001) and TNM stage III patients (P = .004). Moreover, multivariate Cox's proportional hazards regression model analysis revealed that AKIP1 high expression was an independent predictive factor for worse DFS (P < .001) and OS (P < .001).ConclusionTumor tissue AKIP1 expression may have the potential to be a biomarker assisting in disease monitoring and prognosis in NSCLC.