Kinesin Family Member 20A Research Articles

MRNA expression and DNA methylation analysis of the inhibitory mechanism of H2O2 on the proliferation of A549 cells.

Reactive oxygen species, particularly hydrogen peroxide (H2O2), can induce proliferation inhibition and death of A549 cells via oxidative stress. Oxidative stress has effect on DNA methylation. Oxidative stress and DNA methylation feature a common denominator: The one carbon cycle. To explore the inhibitory mechanism of H2O2 on the proliferation of lung cancer cells, the present study analysed the mRNA expression and methylation profiles in A549 cells treated with H2O2 for 24 h, as adenocarcinoma is the most common pathological type of lung cancer. The DNA methylation profile was constructed using reduced representation bisulphite sequencing, which identified 29,755 differentially methylated sites (15,365 upregulated and 14,390 downregulated), and 1,575 differentially methylated regions located in the gene promoters were identified using the methylKit. Analysis of the assocaition between gene expression and methylation levels revealed that several genes were downregulated and hypermethylated, including cyclin-dependent kinase inhibitor 3, denticleless E3 ubiquitin protein ligase homolog, centromere protein (CENP)F, kinesin family member (KIF)20A, CENPA, KIF11, PCNA clamp-associated factor and GINS complex subunit 2, which may be involved in the inhibitory process of H2O2 on the proliferation of A549 cells.

Identification of hub genes associated with esophageal cancer progression using bioinformatics analysis.

The underlying causes of esophageal cancer (EC) are unknown. To explore the molecular mechanisms that lead to EC, gene expression profiles of large cohorts of patients with EC were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus (GEO) databases (GSE5364, GSE20347 and GSE23400). The present study identified 83 upregulated and 22 downregulated genes between EC and normal tissue using R statistical software and the GEO2R web tool. The Database for Annotation, Visualization and Integrated Discovery was used to identify the associated pathways, and for functional annotation of the differentially expressed genes (DEGs). Protein-protein interactions of these DEGs were analyzed based on the Search Tool for the Retrieval of Interacting Genes database, and hub genes were visualized using Cytoscape software. An online Kaplan-Meier plotter survival analysis tool was utilized to evaluate the prognostic value of hub gene expression in patients with EC. Further analysis of an additional dataset from GEO (GSE21293) revealed that these genes were associated with infiltration and metastasis in EC. In addition, the Gene Expression Profiling Interactive Analysis tool was used to evaluate expression levels of hub genes in patients with EC for different pathological stages. The Ualcan analysis tool was used to evaluate the expression levels of hub genes for different histological types. Overall, ubiquitin conjugating enzyme E2 C, cyclin dependent kinase inhibitor 3, CDC28 protein kinase regulatory subunit 2, kinesin family member 20A (KIF20A) and RAD51 associated protein 1 (RAD51AP1) were upregulated in EC tissues compared with normal tissues, and upregulation of these genes was a poor prognostic factor for patients with EC, indicating that these genes may mediate EC cell infiltration and metastasis. Among the hub genes, KIF-20A had potential value for predicting the pathological stage of EC. KIF20A and RAD51AP1 were more informative biomarkers of esophageal squamous cell carcinoma. Further studies are required to explore the value of these genes in the treatment of EC.

Knockdown of circHIPK3 Facilitates Temozolomide Sensitivity in Glioma by Regulating Cellular Behaviors Through miR-524-5p/KIF2A-Mediated PI3K/AKT Pathway.

Background: Temozolomide (TMZ) resistance is a serious hindrance in clinical chemotherapy for glioma. Circular RNA homeodomain interacting protein kinase 3 (circHIPK3) can be involved in regulating the progression of glioma, but the molecular mechanism of circHIPK3 in TMZ-resistant-glioma is completely unclear. Materials and Methods: The levels of circRNA, miRNA, and mRNA were examined using quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay was used for assessing the half inhibitory concentration (IC50) of TMZ and cell proliferation. Cell apoptosis and metastasis (migration and invasion) were detected by flow cytometry and transwell assay, respectively. Western blot and dual-luciferase reporter assay were performed several times to analyze the expression levels of associated proteins and the targeted relation. Results: The upregulation of circHIPK3 was found in TMZ-resistant glioma tissues and cells. Both circHIPK3 knockdown and kinesin family member 2A (KIF2A) inhibition could facilitate TMZ sensitivity and apoptosis but repress proliferation and metastasis in TMZ-resistant glioma cells. CircHIPK3 targeted microRNA-524-5p (miR-524-5p) and KIF2A functioned as a downstream target of miR-524-5p. Decrease of miR-524-5p relieved the effects of si-circHIPK3 on TMZ-resistant glioma cells by upregulating KIF2A. Downregulation of circHIPK3 refrained the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathway partly through miR-524-5p/KIF2A axis. Conclusions: Knockdown of circHIPK3 promoted TMZ sensitivity in glioma by modulating proliferation, metastasis, and apoptosis through miR-524-5p/KIF2A-mediated PI3K/AKT pathway. CircHIPK3 may be the potential target for the diagnosis and therapy of TMZ-resistant glioma.

Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk

Single nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3aK14∆/∆ mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD. Thus, KIF3A is required for skin barrier homeostasis whereby decreased KIF3A skin expression causes disrupted skin barrier function and promotes development of AD.

Cyclin F and KIF20A, FOXM1 target genes, increase proliferation and invasion of ovarian cancer cells

Increased expression of FOXM1 is observed in a variety of human malignancies. The downstream target genes of FOXM1 involved in tumorigenesis and development are not fully elucidated in ovarian cancer. Here, we identified Cyclin F, a substrate recognition subunit of SCF (Skp1-Cul1-F-box protein) complex, and Kinesin Family Member 20A (KIF20A) were transcriptionally regulated by FOXM1 in ovarian cancer. Accordingly, Cyclin F and KIF20A were commonly overexpressed in ovarian cancer. Functionally, forced expression of Cyclin F or KIF20A significantly enhanced while knockdown of them decreased proliferation and invasion of ovarian cancer cells. Importantly, high levels of Cyclin F and KIF20A correlated with poor prognosis in patients with ovarian cancer. Our findings indicate that Cyclin F and KIF20A are functional targets of FOXM1 which might be potential drug targets in ovarian cancer.

Long Non-Coding RNA Paternally Expressed Imprinted Gene 10 (PEG10) Elevates Diffuse Large B-Cell Lymphoma Progression by Regulating Kinesin Family Member 2A (KIF2A) via Targeting MiR-101-3p.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a common malignant tumor in the immune system with high mortality. We investigated the functional effects of long non-coding RNA paternally expressed imprinted gene 10 (PEG10) on DLBCL progression.Material/MethodsReal-time quantitative polymerase chain reaction was used to measure the level of PEG10, kinesin family member 2A (KIF2A) and microRNA-101-3p (miR-101-3p) in DLBCL tissues and cell lines. The relative protein level was detected by western blot analysis. The biological behaviors including cell proliferation, apoptosis, migration, and invasion were determined by MTT assay, flow cytometry analysis, and Transwell assays, respectively. Bioinformatics analysis and dual-luciferase reporter assay were performed to evaluate the interaction among PEG10, miR-101-3p, and KIF2A.ResultsPEG10 and KIF2A level were significantly upregulated, while miR-101-3p was downregulated in DLBCL tissues and cells. PEG10 positively regulated KIF2A level in DLBCL. PEG10, or KIF2A deletion significantly inhibited the proliferative, migratory, and invasive abilities of DLBCL cells and elevated cell apoptosis in DLBCL cells. KIF2A upregulation partially reversed the effects of PEG10 downregulation on cell growth, metastasis, and apoptosis in DLBCL. Moreover, PEG10 negatively regulated miR-101-3p level and miR-101-3p upregulation exerted inhibition effects on the progression of DLBCL. Besides, miR-101-3p was a target of PEG10 and miR-101-3p could directly target KIF2A. PEG10 promoted KIF2A level by sponging miR-101-3p.ConclusionsOur findings revealed that PEG10 played an oncogenic role in DLBCL progression, which might be a potential target for the treatment of DLBCL.

Knockdown of Circ_CCNB2 Sensitizes Prostate Cancer to Radiation Through Repressing Autophagy by the miR-30b-5p/KIF18A Axis.

Background: Circular RNAs (circRNAs) have recently emerged as crucial regulatory molecules in prostate cancer (PCa), but few researches focus on the effects of circRNAs on PCa radiosensitivity. The issue will be addressed in this study using circRNA Cyclin B2 (circ_CCNB2) as an object. Materials and Methods: All RNA and protein levels were severally examined using quantitative real-time polymerase chain reaction and Western blot. Colony formation assay and flow cytometry were implemented for detecting cell colony capacity and apoptotic cells, respectively. Cellular migration and invasion abilities were evaluated by transwell assay. The combination between potential target molecules was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The effect of circ_CCNB2 on PCa radiosensitivity in vivo was explored using xenograft models in mice. Results: Circ_CCNB2 was upregulated in irradiation-resistant PCa tissues and cells. Circ_CCNB2 knockdown had promoted effect on the radiosensitivity of irradiation-resistant PCa cells by inhibiting autophagy. Besides, circ_CCNB2 could directly sponge miR-30b-5p, and the promotion of circ_CCNB2 knockdown on PCa radiosensitivity was achieved by elevating miR-30b-5p. MiR-30b-5p enhanced the radiosensitivity of irradiation-resistant PCa cells through repressing the expression of its target kinesin family member 18A (KIF18A). Furthermore, circ_CCNB2 regulated the KIF18A level through targeting miR-30b-5p. Circ_CCNB2 downregulation facilitated PCa radiosensitivity in vivo through inhibiting autophagy by miR-30b-5p/KIF18A. Conclusions: In this study, knockdown of circ_CCNB2 was shown to promote PCa radiosensitivity through autophagy repression by miR-30b-5p/KIF18A axis, developing a molecular resistance mechanism of PCa radiotherapy and a feasible strategy to increase radiosensitivity.

Screening and Identification of Therapeutic Targets for Pulmonary Arterial Hypertension Through Microarray Technology.

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by vascular cell proliferation; the pathogenesis of PAH has yet to be fully elucidated. Publicly available genetic data were downloaded from the Gene Expression Omnibus (GEO) database, and gene set enrichment analysis (GSEA) was used to determine significant differences in gene expression between tissues with PAH and healthy lung tissues. Differentially expressed genes (DEGs) were identified using the online tool, GEO2R, and functional annotation of DEGs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Next, the construction and module analysis of the protein–protein interaction (PPI) network and verification of the expression level of hub genes was performed. Finally, prediction and enrichment analysis of microRNAs associated with the hub genes was carried out. A total of 110 DEGs were detected by screening PAH and healthy lung samples. The expression of nine genes [polo-like kinase 4 (PLK4), centromere protein U, kinesin family member 20B, structural maintenance of chromosome 2 (SMC2), abnormal spindle microtubule assembly, Fanconi Anemia complementation group I, kinesin family member 18A, spindle apparatus coiled-coil protein 1, and MIS18 binding protein 1] was elevated in PAH; this was statistically significant compared with their expression in healthy lung tissue, and they were identified as hub genes. GO and KEGG analysis showed that the variations in DEGs were abundant in DNA-templated transcription, sister chromatid cohesion, mitotic nuclear division, cell proliferation, and regulation of the actin cytoskeleton. In conclusion, this study has successfully identified hub genes and key pathways of PAH, with a total of 110 DEGs and nine hub genes related to PAH, especially the PLK4 and SMC2 genes, thus providing important clues for the in-depth understanding of the molecular mechanism of PAH and providing potential therapeutic targets.

KIF20A Predicts Poor Survival of Patients and Promotes Colorectal Cancer Tumor Progression through the JAK/STAT3 Signaling Pathway.

Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.

Effect of Sishen Pill on Memory T Cells From Experimental Colitis Induced by Dextran Sulfate Sodium.

Immune memory has a protective effect on the human body, but abnormal immune memory is closely related to the occurrence and development of autoimmune diseases including inflammatory bowel disease (IBD). Sishen Pill (SSP) is a classic prescription of traditional Chinese medicine, which is often used to treat chronic colitis, but it is not clear whether SSP can alleviate experimental colitis by remodeling immune memory. In the present study, the therapeutic effect of SSP on chronic colitis induced by dextran sulfate sodium (DSS) was evaluated by colonic length, colonic weight index, macroscopic and microscopic scores, and pathological observation. The cytokine levels were tested by enzyme-linked immunosorbent assay (ELISA); the percentages of central memory T (Tcm) and effector memory T (Tem) cells were analyze\\d by flow cytometry; and activation of phosphoinositide 3-kinase (PI3K)/Akt signaling proteins was measured by western blotting. After 7-days' treatment, SSP alleviated DSS-induced colitis, which was demonstrated by decreased colonic weight index, colonic weight, histopathological injury scores, restored colonic length, gradual recovery of colonic mucosa, and lower levels of interleukin (IL)-2, IL-7, IL-12, and IL-15, while SSP increased IL-10 expression. SSP obviously regulated the quantity and subpopulation of Tcm and Tem cells. Furthermore, SSP markedly inhibited activation of PI3K, Akt, phospho-Akt, Id2, T-bet, forkhead box O3a, Noxa, and C-myc proteins in the PI3K/Akt signaling pathway and activated Rictor, Raptor, tuberous sclerosis complex (TSC)1, TSC2, phospho-AMP-activated kinase (AMPK)-α, AMPK-α, eukaryotic translation initiation factor 4E-binding protein 2, kinesin family member 2a, and 70-kDa ribosomal protein S6 kinase. These results indicate that SSP effectively controls Tem cells in the peripheral blood to relieve experimental colitis induced by DSS, which were potentially related with inhibiting the PI3K/Akt signaling pathway.

The kinesin motor protein KIF4A as a potential therapeutic target in renal cell carcinoma.

Kinesin family member 4A (KIF4A) is located in the human chromosome band Xq13.1. It has a highly conserved kinesin motor region at its N-terminus, which is followed by a central coiled-coil region and a C-terminus cargo-binding domain that contains a cysteine-rich motif. It is aberrantly expressed in a variety of cancers. Our study aimed to determine the expression of KIF4A in renal cell carcinoma (RCC) and to gain new insights into the underlying molecular mechanisms of this disease. Here, we found that KIF4A expression in RCC specimens increased relative to that in normal renal tissues. A significant correlation existed between the expression of KIF4A and the clinicopathologic features of RCC. Elevated KIF4A expression was associated with poor overall survival and disease-free survival. Univariate and multivariate Cox regression analysis revealed that KIF4A was an independent prognostic factor for poor survival in human patients with RCC. CCK-8 proliferation assay, cell cycle analysis, and subcutaneous tumor formation analysis in nude mice consistently showed that KIF4A promoted RCC proliferation. Our findings also indicated that KIF4A functions as an accelerator of RCC metastasis as certified through transwell chamber analysis, wound healing assay, and angiogenesis assay. The expression levels of cyclin D1, cyclin E2, matrix metalloproteinase-2, matrix metalloproteinase-9, hypoxia-inducible factor 1α, and vascular endothelial growth factor in the KIF4A knockdown group were lower than those in the control group and were consistent with those in classic oncogenic pathways. These findings implied that the expression of KIF4A was significantly related to the tumor incidence, metastasis, and prognosis of patients with RCC. Our work provides new breakthroughs for the diagnosis and treatment of RCC.

Characterization of KIF20A as a prognostic biomarker and therapeutic target for different subtypes of breast cancer.

The aim of the present study was to identify novel prognostic biomarkers and therapeutic targets for breast cancer; thus, genes that are frequently overexpressed in several types of breast cancer were screened. Kinesin family member20A (KIF20A) was identified as a candidate molecule during this process. Immunohistochemical staining performed using tissue microarrays from 257samples of different breast cancer subtypes revealed that KIF20A was expressed in195 (75.9%) of these samples, whereas it was seldom expressed in normal breast tissue. KIF20A protein was expressed in all types of breast cancer observed. However, it was more frequently expressed in human epidermal growth factor receptor2 (HER2)‑positive and triple‑negative breast cancer than in the luminal type. Moreover, KIF20A expression was significantly associated with the poor prognosis of patients with breast cancer. A multivariate analysis indicated that KIF20A expression was an independent prognostic factor for patients with breast cancer. The suppression of endogenous KIF20A expression using small interfering ribonucleic acids or via treatment with paprotrain, a selective inhibitor of KIF20A, significantly inhibited breast cancer cell growth through cell cycle arrest at the G2/M phase and subsequent mitotic cell death. These results suggest that KIF20A is a candidate prognostic biomarker and therapeutic target for different types of breast cancer.

The Overexpression of Kinesin Superfamily Protein 2A (KIF2A) was Associated with the Proliferation and Prognosis of Esophageal Squamous Cell Carcinoma.

AimKinesin family member 2A (KIF2A) is a member of the kinesin-13 superfamily protein. KIF2A played a role in the development of many tumors. However, the role of KIF2A in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to investigate the role of KIF2A in ESCC.MethodsWe used bioinformatics analysis to study the expression levels and prognosis of KIF2A in ESCC and normal tissues. We also used our own samples to verify the results by immunohistochemistry. Then, the biological functions of KIF2A in ESCC was studied by cell experiments and animal experiments.ResultsBoth the TCGA database and our samples showed that KIF2A was relatively highly expressed in ESCC tissues and was significantly associated with disease-free survival (P =0.037) in TCGA database. Colony formation assay, CCK8 and Western blotting results showed that knockdown of KIF2A can significantly reduce colony forming ability and proliferation ability. The results of animal experiments showed that knocking down KIF2A can significantly reduce the tumor volume of mice.ConclusionKIF2A might be used as a prognostic factor for ESCC, and knockdown of KIF2A could inhibit ESCC proliferation in vitro and in vivo, respectively. KIF2A could serve as a potential prognostic biomarker and therapeutic target for future ESCC.

Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus.

The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP‐competitive mitotic kinesin KIF18A inhibitor BTB‐1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB‐1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran‐binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB‐1 greatly improved the viability of IAV‐infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.

Functional Alterations in Ciliogenesis-Associated Kinase 1 (CILK1) that Result from Mutations Linked to Juvenile Myoclonic Epilepsy.

Ciliopathies are a group of human genetic disorders associated with mutations that give rise to the dysfunction of primary cilia. Ciliogenesis-associated kinase 1 (CILK1), formerly known as intestinal cell kinase (ICK), is a conserved serine and threonine kinase that restricts primary (non-motile) cilia formation and length. Mutations in CILK1 are associated with ciliopathies and are also linked to juvenile myoclonic epilepsy (JME). However, the effects of the JME-related mutations in CILK1 on kinase activity and CILK1 function are unknown. Here, we report that JME pathogenic mutations in the CILK1 N-terminal kinase domain abolish kinase activity, evidenced by the loss of phosphorylation of kinesin family member 3A (KIF3A) at Thr672, while JME mutations in the C-terminal non-catalytic domain (CTD) have little effect on KIF3A phosphorylation. Although CILK1 variants in the CTD retain catalytic activity, they nonetheless lose the ability to restrict cilia length and also gain function in promoting ciliogenesis. We show that wild type CILK1 predominantly localizes to the base of the primary cilium; in contrast, JME variants of CILK1 are distributed along the entire axoneme of the primary cilium. These results demonstrate that JME pathogenic mutations perturb CILK1 function and intracellular localization. These CILK1 variants affect the primary cilium, independent of CILK1 phosphorylation of KIF3A. Our findings suggest that CILK1 mutations linked to JME result in alterations of primary cilia formation and homeostasis.

KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo.

PurposeTo evaluate the expression in human clear cell renal cell carcinoma (ccRCC) tissues and explore the effects of kinesin family member 4A (KIF4A) on ccRCC progression.MethodsGEPIA was used to evaluate the mRNA levels of KIF4A in human ccRCC tissues from TCGA database, and Immunohistochemistry (IHC) assays were performed to assess its expression in human ccRCC tissues collected in our hospital. The clinical-pathological analysis was performed to explore the correlation with KIF4A expression. The effects of KIF4A on ccRCC cell proliferation were detected through colony formation and MTT assays. Finally, the effects of KIF4A on tumor growth were measured using a mice model.ResultsBioinformation results showed the expression of KIF4A mRNA was upregulated in ccRCC tissues and high expression of KIF4A was related with poor prognosis in ccRCC patients. We also found a high expression of KIF4A in human ccRCC tissues collected in our hospital. We also found its expression level was correlated with clinical characteristics, including T stage (P=0.035*) and lymphatic metastasis (P=0.028*). We further confirmed that knockdown of KIF4A suppressed cell proliferation in HTB-47 and CRL-1932 cells. Furthermore, KIF4A contributes to tumor growth of ccRCC cells in mice.ConclusionWe found the abnormal high expression of KIF4A in human ccRCC tissues and demonstrated that KIF4A could serve as a tumor induction gene.

Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex.

The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling.Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation.Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R on ACTA2.Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.

Knockdown of Kif20a inhibits growth of tumors in soft tissue sarcoma in vitro and in vivo

Kif20a (Kinesin Family Member 20A), plays a role in cell mitosis, cell migration and intracellular transport. Numerous studies have demonstrated that Kif20a is abnormally highly expressed in a variety of tumors and shows poor prognosis. Soft tissue sarcoma (STS) represents a group of malignant tumors with poor prognosis. The role of Kif20a in STSs has not been systematically studied. In the present study, bioinformatics analysis, in vitro and in vivo experiments were conducted to investigate the function of Kif20a in STSs. In bioinformatics analysis higher KIf20a expression indicated a poor prognosis. Functional enrichment analysis indicated that Kif20a may be related to cell cycle, p53 and other signaling pathways. In vitro experiments showed that after the down-regulation of Kif20a, cell proliferation, migration and invasion were decreased, while apoptosis was increased. In vivo experiments revealed that Kif20a affected the proliferation of tumors in tumor-bearing mice. In summary, our findings revealed that Kif20a performs an important role in STS, indicating that it is a potential prognostic biomarker and potentially representing a therapeutic target for the disease.

Kinesin family member 2A high expression correlates with advanced tumor stages and worse prognosis in non-small cell lung cancer patients.

BackgroundThis present study was to explore the association of kinesin family member 2A (KIF2A) expression with clinicopathological features and survival profiles, and the effect of KIF2A on cell proliferation and chemosensitivity in non‐small cell lung cancer (NSCLC).MethodsTumor and paired adjacent specimens were collected from 380 patients with NSCLC underwent resection for immunohistochemistry assay of KIF2A expression. In vitro, the effect of KIF2A on cell proliferation, chemosensitivity to cisplatin/vinorelbine was detected via KIF2A plasmids transfection into NCI‐H1299 NSCLC cells.ResultsKinesin family member 2A expression was upregulated in tumor tissues compared with adjacent tissues, and tumor tissue KIF2A high expression was associated with higher pathological grade (P < .001), larger tumor size (P = .021), lymph node metastasis (P = .044), and increased tumor‐node‐metastasis stage (P = .001). As for survival profiles, disease‐free survival (P < .001) and overall survival (P < .001) were worse in patients with KIF2A high expression compared with those with KIF2A low expression. Multivariate Cox's regression exhibited that KIF2A high expression was an independent predictive factor for lower DFS (P < .001) and OS (P < .001). In vitro, KIF2A promoted proliferation and decreased chemosensitivity to cisplatin but not vinorelbine in NCI‐H1299 NSCLC cells.ConclusionsThe correlation of KIF2A expression with tumor features, survival, and its cellular function implies its potential as a prognostic biomarker and a treatment target in NSCLC.

KIF20A promotes cellular malignant behavior and enhances resistance to chemotherapy in colorectal cancer through regulation of the JAK/STAT3 signaling pathway.

Background/Aims: Kinesin family member 20A (KIF20A) is upregulated in multiple cancers and plays important roles in promoting malignant behavior, whereas its exact role in CRC remains unknown.Results: Both genomic and protein expression levels showed that KIF20A was upregulated in CRC. Further functional analyses revealed that KIF20A had a crucial role in improving cell proliferation and resistance to chemotherapy in CRC. Finally, we provided distinct mechanistic evidence that KIF20A achieved all of its pathological functions in CRC by activating the JAK/STAT3 pathway.Conclusion: Our results suggested that KIF20A regulated a set of malignant characteristics in CRC by activating the JAK/STAT3 pathway. Our findings indicate a new direction for the development of more effective therapeutic treatments for CRC.Methods: Three Gene Expression Omnibus datasets and The Cancer Genome Atlas datasets were used to investigate the expression level of KIF20A in CRC. Further experiments included immunohistochemical staining, western blot analysis, qRT-PCR, gene silencing, and a cell-injected xenograft mouse model to investigate the interaction between KIF20A and the JAK/STAT3 signaling pathway in both patient-derived specimens and CRC cell lines.