Spindle And Kinetochore-associated Protein 1 Research Articles

Decreased mononuclear cell NR3C1 SKA2 and FKPB5 expression levels among adult survivors of suicide bombing terror attacks in childhood are associated with the development of PTSD.

Life threatening trauma and the development of PTSD during childhood, may each associate with transcriptional perturbation of immune cell glucocorticoid reactivity, yet their separable longer term contributions are less clear. The current study compared resting mononuclear cell gene expression levels of the nuclear receptor, subfamily 3, member 1 (NR3C1) coding the glucocorticoid receptor, its trans-activator spindle and kinetochore-associated protein 2 (SKA2), and its co-chaperon FKBP prolyl isomerase 5 (FKBP5), between a cohort of young adults first seen at the Hadassah Emergency Department (ED) after surviving a suicide bombing terror attack during childhood, and followed longitudinally over the years, and matched healthy controls not exposed to life threatening trauma. While significant reductions in mononuclear cell gene expression levels were observed among young adults for all three transcripts following early trauma exposure, the development of subsequent PTSD beyond trauma exposure, accounted for a small but significant portion of the variance in each of the three transcripts. Long-term perturbation in the expression of immune cell glucocorticoid response transcripts persists among young adults who develop PTSD following life threatening trauma exposure in childhood, denoting chronic dysregulation of immune stress reactivity.

Circ_0001387 regulates SKA2 to accelerate breast cancer progression through miR-136-5p.

Growing evidence has revealed the critical regulatory role for circular RNAs (circRNAs) in cancer. This study aimed to explore the function of circ_0001387 in breast cancer (BC). Circ_0001387, miR-136-5p, and spindle and kinetochore-associated protein 2 (SKA2) levels were analyzed by quantitative real-time polymerase chain reaction. Clone formation and 5-ethynyl-2'-deoxyuridine assays were used to analyze cell proliferation. Cell apoptosis and cell migration and invasion abilities were analyzed using flow cytometry or transwell assay. Mechanism assay was used to confirm the association between miR-136-5p and circ_0001387 or SKA2. The effect of circ_0001387 on tumor growth in vivo was analyzed by the xenograft mice model. Circ_0001387 and SKA2 were expressed at high levels, whereas miR-136-5p was lowly expressed in BC tissues and cells. Meanwhile, the downregulation of circ_0001387 restrained BC cell progression in vitro and in vivo. Circ_0001387 competitively bound to miR-136-5p to regulate BC cell malignant behaviors. SKA2 was targeted by miR-136-5p, and SKA2 reinstated the suppressive effect of miR-136-5p upregulation in BC cells. Our study indicated that circ_0001387 contributed to BC cell progression through miR-136-5p/SKA2 axis.

SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma.

The most hostile form of urologic cancer, clear cell renal cell carcinoma (ccRCC), has a high fatality rate and poor prognosis due to tumor metastasis at initial presentation. The complex process driving ccRCC metastasis is still unknown, though. In this study, we demonstrate that Spindle and kinetochore-associated protein 1 (SKA1) expression is significantly upregulated in ccRCC tissues and associated with aggressive clinicopathologic characteristics. Functionally, SKA1 knockdown on ccRCC cells reduced cancer cell motility both in vivo and in vitro research. These bioactivities of SKA1 may be brought on by its specific interaction with scaffold attachment factor B, according to the proposed mechanism (SAFB), which could further depress the transcription of dual specificity phosphatase 6 (DUSP6). Our findings may provide a new way of researching SKA1-regulated tumor metastasis, and indicate that SKA1 is a prospective therapeutic target for renal carcinoma.

Resting mononuclear cell NR3C1 and SKA2 expression levels predict blunted cortisol reactivity to combat training stress among elite army cadets exposed to childhood adversity.

Childhood adversity (CA) may alter reactivity to stress throughout life, increasing risk for psychiatric and medical morbidity, yet long-term correlates of milder CA levels among high functioning healthy adolescents are less studied. The current study examined the prevalence and impact of CA exposure among a cohort of healthy motivated elite parachute unit volunteers, prospectively assessed at rest and at the height of an intensive combat-simulation exposure. We found significantly reduced gene expression levels in resting mononuclear cell nuclear receptor, subfamily 3, member 1 (NR3C1), and its transactivator spindle and kinetochore-associated protein 2 (SKA2), that predict blunted cortisol reactivity to combat-simulation stress among CA exposed adolescents. Long-term alterations in endocrine immune indices, subjective distress, and executive functions persist among healthy high functioning adolescents following milder CA exposure, and may promote resilience or vulnerability to later real-life combat exposure.

Circ_0008039 supports breast cancer cell proliferation, migration, invasion, and glycolysis by regulating the miR-140-3p/SKA2 axis.

Circular RNAs (circRNAs) have been shown to modulate gene expression and participate in the development of multiple malignancies. The purpose of this study was to investigate the role of circ_0008039 in breast cancer (BC). The expression of circ_0008039, miR-140-3p, and spindle and kinetochore-associated protein 2 (SKA2) was detected by qRT-PCR. Cell viability, colony formation, migration, and invasion were evaluated using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, colony formation assay, and transwell assay, respectively. Glucose consumption and lactate production were measured using commercial kits. Protein levels of hexokinase II (HK2) and SKA2 were determined by western blot. The interaction between miR-140-3p and circ_0008039 or SKA2 was verified by dual-luciferase reporter assay. Finally, a mouse xenograft model was established to investigate the roles of circ_0008039 in BC in vivo. We found that circ_0008039 and SKA2 were upregulated in BC tissues and cells, while miR-140-3p was downregulated. Knockdown of circ_0008039 suppressed BC cell proliferation, migration, invasion, and glycolysis. Moreover, miR-140-3p could bind to circ_0008039 and its inhibition reversed the inhibitory effect of circ_0008039 interference on proliferation, migration, invasion, and glycolysis in BC cells. SKA2 was verified as a direct target of miR-140-3p and its overexpression partially inhibited the suppressive effect of miR-140-3p restoration in BC cells. Additionally, circ_0008039 positively regulated SKA2 expression by sponging miR-140-3p. Consistently, silencing circ_0008039 restrained tumor growth via increasing miR-140-3p and decreasing SKA2. In conclusion, circ_0008039 downregulation suppressed BC cell proliferation, migration, invasion, and glycolysis partially through regulating the miR-140-3p/SKA2 axis, providing an important theoretical basis for treatment of BC.

Spindle and kinetochore-associated protein 2 facilitates the proliferation and invasion of hepatocellular carcinoma via the regulation of Wnt/β-catenin signaling

Recent studies have shown that spindle and kinetochore-associated protein 2 (SKA2) is dysregulated in multiple tumors and acts as a key regulator of tumor progression. However, whether SKA2 plays a role in hepatocellular carcinoma (HCC) has not been fully elucidated. The purpose of this study was to explore the expression, function and underlying molecular mechanism of SKA2 in HCC. We found that SKA2 was highly expressed in HCC tissues and cell lines. Knockdown of SKA2 caused marked reductions in the proliferative, colony-forming and invasive capacities of HCC cells, while SKA2 overexpression had opposite effects. Further experiments revealed that overexpression of SKA2 enhanced expression levels of phosphorylated glycogen synthase kinase-3β (GSK-3β) and active β-catenin in HCC cells. Moreover, SKA3 overexpression enhanced transcriptional activity mediated by Wnt/β-catenin signaling. Knockdown of SKA3 downregulated the activation of Wnt/β-catenin signaling, and the effect was significantly reversed by the inhibition of GSK-3β. Notably, inhibition of Wnt/β-catenin signaling markedly abrogated SKA2-mediated promotion effect on HCC proliferation and invasion. In addition, knockdown of SKA2 impeded tumor formation and growth in HCC cells in a nude mouse in vivo model. Overall, these findings indicate that SKA2 accelerates the progression of HCC through the upregulation of Wnt/β-catenin signaling. Our study highlights a potential role of SKA2 in HCC progression and suggests it as a possible target for HCC treatment.

SKA1 regulates actin cytoskeleton remodelling via activating Cdc42 and influences the migration of pancreatic ductal adenocarcinoma cells.

ObjectivesSpindle and kinetochore–associated protein 1(SKA1), originally identified as a protein essential for proper chromosome segregation, has been recently linked to multiple malignancies. This study aimed to explore the biological, clinical role and molecular mechanism of SKA1 in pancreatic carcinogenesis.Materials and MethodsSKA1 expression was detected in 145 pancreatic ductal adenocarcinoma (PDAC) specimens by immunohistochemistry. Biological behaviour assays were used to determine the role of SKA1 in PDAC progression in vitro and in vivo. Using isobaric tags for relative and absolute quantitation (iTRAQ), SKA1’s downstream proteins were examined. Moreover, cytochalasin B and ZCL278 were used to explore the changes of SKA1‐induced signalling and cell morphology, with further confirmation by immunoblotting and immunofluorescence assays.ResultsIncreased SKA1 expression was significantly correlated with tumour size and cellular differentiation degree in PDAC tissues. Furthermore, elevated levels of SKA1 reflected shorter overall survival (P = .019). As for biological behaviour, SKA1 acted as a tumour promotor in PDAC, overexpression of SKA1 facilitates cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, we demonstrated that SKA1 enhanced pancreatic cancer aggressiveness by inhibiting G2/M arrest and regulating actin cytoskeleton organization via activating Cdc42.ConclusionsThis study revealed novel roles for SKA1 as an important regulator of actin cytoskeleton organization and an oncogene in PDAC cells, which may provide insights into developing novel therapeutics.

SKA1 overexpression is associated with theprognosis of esophageal squamous cell carcinoma and regulates cell proliferation and migration.

Spindle and kinetochore‑associated protein1 (SKA1), a microtubule‑binding subcomplex of the outer kinetochore, is essential for complete chromosomal separation. SKA1 has been suggested as a potential biomarker for various types of cancer. However, the exact role of SKA1 in esophageal squamous cell carcinoma (ESCC) remains unclear. The present study investigated whether SKA1 affects the biological behavior of ESCC. The expression of SKA1 in ESCC tissues was measured using immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction. In addition, a SKA1‑silencing lentivirus was constructed, which was transfected into TE‑1 cells to establish stable SKA1‑knockdown TE‑1 cells. Proliferation was analyzed using a Celigo image cytometer and a MTS assay. Cell cycle progression and apoptosis were analyzed by flow cytometry, while cell migration was assessed using a Transwell assay. SKA1 was significantly overexpressed in ESCC tissues, and SKA1 overexpression was significantly associated with differentiation, pathological N stage and pathological tumor‑node‑metastasis stage. SKA1 was determined to be an independent prognostic factor for ESCC. Furthermore, SKA1 was significantly overexpressed in ESCC cells, and SKA1‑silencing inhibited cell proliferation and migration, arrested the cell cycle and promoted cell apoptosis. In summary, SKA1 may serve as a potential therapeutic target and prognostic biomarker for ESCC.

Long non-coding RNA ZFAS1 promotes proliferation and metastasis of clear cell renal cell carcinoma via targeting miR-10a/SKA1 pathway

BackgroundLncRNA ZFAS1 (ZNFX1 antisense RNA1) plays key roles in the occurrence and progression of various cancers, including colorectal cancer, glioma, lung cancer, gastric cancer, and so on. To date, relatively little is known about its potential role in development and/or progression of clear cell renal cell carcinoma (ccRCC). MethodsExpression level of ZFAS1 and miR-10a in 60 ccRCC and 20 adjacent non-tumor tissues were determined by using qRT-PCR. The effect of knockdown of ZFAS1 on cell proliferation, migration and invasion were measured by CCK-8 assay, transwell migration and invasion assay, respectively. The correlation of ZFAS1 and miR-10a was analyzed by bioinformatics DIANA TOOLS. Protein and mRNA expression of spindle and kinetochore-associated protein 1(SKA1) were determined by western blot and qRT-PCR analysis, respectively. Interactions between ZFAS1 and miR-10a were verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay, and interactions between miR-10a and SKA1 was verified by a luciferase reporter assay. ResultsWe observed that high-level expression of ZFAS1 is positively correlated with poor prognosis and shorter overall survival (OS) in patients with ccRCC. Knockdown of ZFAS1 significantly suppressed proliferation, migration and invasion of ccRCC cells. Furthermore, miR-10a was identified as a target of ZFAS1. Silencing miR-10a could attenuate the ability of ZFAS1 in promoting proliferation and metastasis of ccRCC. Subsequently, our studies validated that SKA1, as a key downstream target protein for miR-10a, is responsible for the biological role of ZFAS1. ZFAS1 positively regulated SKA1 expression via sponging miR-10a. ConclusionsTaken together, our findings suggest that ZFAS1 promotes growth and metastasis of ccRCC via targeting miR-10a/SKA1 pathway, which may represent a novel therapeutic target or biomarker for ccRCC.

SKA2 mediates invasion and metastasis in human breast cancer via EMT.

Spindle and kinetochore‑associated protein 2 (SKA2) is essential for regulating the progression of mitosis. In recent years, SKA2 upregulation has been detected in various human malignancies and the role of SKA2 in tumorigenesis has received increasing attention. However, the expression and functional significance of SKA2 in breast cancer are not completely understood. To study the effects of SKA2 on breast cancer, the expression levels of SKA2 in breast cancer tissues and cell lines were evaluated by western blotting, reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining. The results demonstrated that SKA2 expression was increased in breast cancer tissues and cells, and SKA2 overexpression was associated with clinical stage and lymph node metastasis. Functional investigations revealed that SKA2 knockdown in breast cancer cells significantly reduced migration and invasion, and resulted in the decreased expression levels of matrix metalloproteinase (MMP)2 and MMP9. Furthermore, the typical microtubule arrangement was altered in SKA2 small interfering RNA (siSKA2)‑transfected cells. Reduced levels of SKA2 also downregulated the expression of epithelial‑mesenchymal transition proteins, including fibronectin, N‑cadherin and vimentin, whereas there were no alterations in the protein expression levels of E‑cadherin. Conversely, upregulation of SKA2 decreased the expression levels of E‑cadherin, and increased N‑cadherin, fibronectin and vimentin levels. Notably, it was demonstrated that E‑cadherin was translocated from the cytoplasm to the nucleus in siSKA2‑transfected cells. These results demonstrated that SKA2 may be associated with breast cancer metastasis, and siSKA2 inhibited the invasion and metastasis of breast cancer via translocation of E‑cadherin from the cytoplasm to the nucleus.

High expression of spindle and kinetochore- associated protein 1 predicts early recurrence and progression of non-muscle invasive bladder cancer.

Spindle and kinetochore-associated protein 1 (SKA1) is a component of SKA, which is essential for proper chromosome segregation. Recently, SKA1 was found to be over-expressed in several types of human cancers. However, reports on the relationship between SKA1 expression and the prognosis of bladder cancer, in particular, are lacking. To clarify the clinical significance of SKA1 as a prognostic biomarker for early recurrence and progression of patients with non-muscle invasive bladder cancer (NMIBC). The differential expression levels of SKA1 of 148 NMIBC tissues were determined by immunohistochemical staining. Quantitative real-time PCR and western blot analysis were further performed to confirm the immunohistochemistry results. Recurrence and progression free interval were assessed by Kaplan-Meier method and differences between groups calculated by log-rank statistics. The prognostic value of SKA1 for early recurrence and progression was analyzed by multivariate Cox proportional hazard regression models. SKA1 expression was significantly different in various NMIBC tissues. Kaplan-Meier analysis revealed that patients with high SKA1 expression showed high early recurrence (p< 0.001) and progression (p< 0.05) rates. Although univariate Cox regression analysis revealed that several other factors had an impact on recurrence and progression, upon multivariate analysis, high SKA1expression was the only independent predictor for early recurrence (hazards ratio [HR], 0.246; 95% confidence interval [CI], 0.131-0.461; p= 0.000) and progression (HR, 0.194; 95% CI, 0.052-0.715; p= 0.014). High SKA1 expression is associated with early recurrence and progression in patients with NMIBC, indicating SKA1 may serve as a promising prognostic biomarker for this disease.

Regulation of spindle and kinetochore-associated protein 1 by antitumor miR-10a-5p in renal cell carcinoma.

Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA‐10a‐5p (miR‐10a‐5p) was significantly downregulated in RCC specimens. The aims of the present study were to investigate the antitumor roles of miR‐10a‐5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR‐10a‐5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKI). Ectopic expression of miR‐10a‐5p in RCC cell lines (786‐O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore‐associated protein 1 (SKA1) was identified as an antitumor miR‐10a‐5p target by genome‐based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI‐treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR‐10a‐5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR‐10a‐5p and overexpression of the SKA1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC.

GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.

We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = -0.48, SE = 0.12, t = -4.02, adjusted P = .004). We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior.

Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2.

Emerging evidence shows that the aberrantly expressed cyclic AMP responsive element-binding protein (CREB) is associated with tumor development and progression in several cancers. Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progress of mitosis. In this study, we evaluate in vitro and in vivo the functional relationship between CREB and SKA2 in renal cell carcinoma (RCC). Suppressing and replenishing CREB levels were used to manipulate SKA2 expression, observing the effects on RCC cell lines. Computational prediction and ChIP assay identified that CREB targeted ska2 by binding its CRE sequence in the human genome. Overexpression of CREB reversed the inhibited cell growth following siSKA2 treatment, and reduced the number of cells holding in mitosis. Decreased expression of CREB suppressed RCC cell growth and xenograft tumor formation, accompanied by reduced expression of SKA2. In RCC tumor samples from patients, mRNA for SKA2 were plotted near those of CREB in each sample, with significantly increased immunohistochemical staining of higher SKA2 and CREB in the higher TNM stages. The study adds evidence that CREB, a tumor oncogene, promotes RCC proliferation. It probably achieves this by increasing SKA2 expression.

Peroxisome proliferator-activated receptor-α-mediated transcription of miR-301a and miR-454 and their host gene SKA2 regulates endothelin-1 and PAI-1 expression in sickle cell disease.

Endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1) play important roles in pulmonary hypertension (PH) in sickle cell disease (SCD). Our previous studies show higher levels of placenta growth factor (PlGF) in SCD correlate with increased plasma levels of ET-1, PAI-1, and other physiological markers of PH. PlGF-mediated ET-1 and PAI-1 expression occurs via activation of hypoxia-inducible factor-1α (HIF-1α). However, relatively little is understood regarding post-transcriptional regulation of PlGF-mediated expression of ET-1 and PAI-1. Herein, we show PlGF treatment of endothelial cells reduced levels of miR-301a and miR-454 from basal levels. In addition, both miRNAs targeted the 3'-UTRs of ET-1 and PAI-1 mRNAs. These results were corroborated in the mouse model of SCD [Berkeley sickle mice (BK-SS)] and in SCD subjects. Plasma levels of miR-454 in SCD subjects were significantly lower compared with unaffected controls, which correlated with higher plasma levels of both ET-1 and PAI-1. Moreover, lung tissues from BK-SS mice showed significantly reduced levels of pre-miR-301a and concomitantly higher levels of ET-1 and PAI-1. Furthermore, we show that miR-301a/miR-454 located in the spindle and kinetochore-associated protein-2 (SKA2) transcription unit was co-transcriptionally regulated by both HIF-1α and peroxisome proliferator-activated receptor-α (PPAR-α) as demonstrated by SKA2 promoter mutational analysis and ChIP. Finally we show that fenofibrate, a PPAR-α agonist, increased the expression of miR-301a/miR-454 and SKA2in human microvascular endothelial cell line (HMEC) cells; the former were responsible for reduced expression of ET-1 and PAI-1. Our studies provide a potential therapeutic approach whereby fenofibrate-induced miR-301a/miR-454 expression can ameliorate PH and lung fibrosis by reduction in ET-1 and PAI-1 levels in SCD.

Downregulation of SKA1 Gene Expression Inhibits Cell Growth in Human Bladder Cancer.

Spindle and kinetochore-associated protein 1 (SKA1), a component of microtubule-binding complex of kinetochore, is essential for proper chromosome segregation. Recently, SKA1 has been shown to be involved in malignant progression of several human cancers. However, its role in bladder cancer is still unknown. To evaluate the function of SKA1 in bladder cancer cells, the authors employed an RNA interference lentivirus system to deplete its expression in both BT5637 and T-24 bladder cancer cells. The cell proliferation was significantly decreased in both cell lines after SKA1 knockdown. Moreover, the colony formation capacity was impaired by SKA1 silencing. Flow cytometry analysis showed that depletion of SKA1 led to cell cycle arrest at S phase. Furthermore, knockdown of SKA1 in T-24 cells obviously downregulated the expressions of CDK4 and Cyclin D1, and alleviated the activations of ERK2 and AKT, conducive to cell growth inhibition. These findings suggested that knockdown of SKA1 could potently suppress bladder cancer cell proliferation in vitro and lentivirus-mediated silencing of SKA1 might serve as a novel strategy for gene therapy of bladder cancer.

Lentivirus-mediated silencing of spindle and kinetochore-associated protein 1 inhibits the proliferation and invasion of neuronal glioblastoma cells

Spindle and kinetochore‑associated protein 1 (SKA1) is an important component of the human kinetochore, which plays a key role in mitosis. The resent study was designed to investigate the role of SKA1 in human glioblastoma. The results of the present study demonstrated that SKA1 was expressed in human glioblastoma cells. In addition, the knockdown of SKA1 expression in the A172 and U251 human glioblastoma cell lines was accomplished using a lentivirus infection method. An MTT assay demonstrated that downregulation of SKA1 may inhibit cell proliferation, without affecting the cell cycle. Furthermore, knockdown of SKA1 expression resulted in reduced cell invasion. The results of the present study indicated that SKA1 may be a potential target protein for antiproliferative and anti‑invasive therapeutic strategies of human glioblastoma.

Expression of Spindle and Kinetochore-Associated Protein 1 Is Associated with Poor Prognosis in Papillary Thyroid Carcinoma.

Aim. Spindle and kinetochore-associated protein 1 (SKA1) is one subtype of SKA, whose protein can make spindle microtubules attach steadily to the kinetochore in the middle of mitosis. At present, there are fewer researches on the relationship between SKA1 expression and tumor development. Methods. In this study, immunohistochemical analysis was used to determine the expression of SKA1 in papillary thyroid carcinoma (PTC) and adjacent tissues. We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis to further verify the results. Results. We found that SKA1 expression was significantly higher in PTC tissues than normal adjacent tissues (P < 0.05). There existed a significant correlation among a higher SKA1 expression, including lymphoid node (P = 0.005), clinical stage (P = 0.015), and extrathyroid invasion (P = 0.004). Survival analysis showed high SKA1 expression in PTC patients more likely to relapse after surgery. Conclusion. High SKA1 expression is predictive of poor prognosis of PTC, implying that SKA1 may be a promising new target for targeted therapies for PTC.

Spindle and kinetochore-associated protein 1 is overexpressed in gastric cancer and modulates cell growth

Spindle and kinetochore-associated protein 1 (SKA1) is a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. SKA1 is required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. Recently, SKA1 has been highlighted as a biomarker in some types of cancers, however, the precise role of SKA1 in gastric cancer remains unknown. In order to investigate the role of SKA1 in gastric cancer, the expression levels of SKA1 were analyzed in 56 gastric cancer samples and 54 non-neoplastic samples by immunohistochemistry, and we found SKA1 was significantly overexpressed in gastric cancer tissues. Moreover, we employed lentivirus-mediated short hairpin RNA to knockdown SKA1 in the human gastric cancer cell line MGC80-3. Functional analysis indicated that SKA1 silencing significantly inhibited cell proliferation and colony formation, as determined by MTT and colony formation assays. The depletion of SKA1 in MGC80-3 cells also led to S phase cell cycle arrest. These results suggest that SKA1 could be used for gastric cancer early diagnosis as a biomarker. It is possible to enable a potential therapy based on targeting SKA1.