Kinesin Family Member 2C Research Articles

Whole-genome resequencing of grass carp (Ctenopharyngodon idella) for genome-wide association study on GCRV resistance

Grass carp (Ctenopharyngodon idella) is a highly productive freshwater fish species that annually contributes significant economic value to the aquaculture industry. However, its production is frequently affected by grass carp haemorrhagic disease (GCHD), which is caused by grass carp reovirus (GCRV). To elucidate the molecular mechanism of GCRV resistance in C. idella, whole-genome resequencing of both susceptible and resistant C. idella was conducted, yielding a total of 3,941,776 high quality single nucleotide polymorphisms (SNPs). A genome-wide association study (GWAS) then identified five significant SNPs, located on chromosomes 2, 3, 5, 6 and 10, associated with the trait of GCRV resistance. An integrative analysis of the GWAS and a previous transcriptome study was performed, and five common genes were identified, including b4galt2 (β-1,4-galactosyltransferase 2), kif2c (Kinesin family member 2C), jmjd8 (JmjC domain containing 8), selenom (Selenoprotein M), and znfx1 (Zinc finger NFX1-type containing 1). This study serves as a valuable basis for implementing marker-assisted selection (MAS) to improve GCRV resistance in C. idella breeding programs, and provides insight into developing methods to control the spread of GCHD.

MEF2C contributes to axonal branching by regulating Kif2c transcription.

Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.

KIF2C as a potential therapeutic target: insights from lung adenocarcinoma subtype classification and functional experiments.

Objective: this study evaluates the prognostic relevance of gene subtypes and the role of kinesin family member 2C (KIF2C) in lung cancer progression. Methods: high-expression genes linked to overall survival (OS) and progression-free interval (PFI) were selected from the TCGA-LUAD dataset. Consensus clustering analysis categorized lung adenocarcinoma (LUAD) patients into two subtypes, C1 and C2, which were compared using clinical, drug sensitivity, and immunotherapy analyses. A random forest algorithm pinpointed KIF2C as a prognostic hub gene, and its functional impact was assessed through various assays and in vivo experiments. Results: The study identified 163 key genes and distinguished two LUAD subtypes with differing OS, PFI, pathological stages, drug sensitivity, and immunotherapy response. KIF2C, highly expressed in the C2 subtype, was associated with poor prognosis, promoting cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), with knockdown reducing tumor growth in mice. Conclusion: The research delineates distinct LUAD subtypes with significant clinical implications and highlights KIF2C as a potential therapeutic target for personalized treatment in LUAD.

Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway.

In the treatment of unresectable advanced hepatocellular carcinoma (HCC), cisplatin is administered transhepatic arterially for local treatment, but the clinical application of cisplatin drugs is frequently hindered by the emergence of drug resistance. Kinesin family member 2C( KIF2C ) has been shown as oncogene in a variety of tumors. Nevertheless, its effect on cisplatin sensitivity has yet to be ascertained. Herein, we aim to investigate the impact of the KIF2C gene on cisplatin sensitivity within HCC and the plausible underlying molecular mechanism. We examined the expression level of the KIF2C gene in HCC cells by real-time quantitative reverse transcription PCR and Western blot analysis, and analyzed bioinformatically by The Gene Expression Omnibus database and The Cancer Genome Atlas database. The KIF2C gene was silenced using the small interfering RNA technology, and its effect on cisplatin drug sensitivity in HCC cells was evaluated by flow cytometry, cell proliferation, cell migration, and invasion assays. Our results indicated that KIF2C was highly expressed in HCC cells. KIF2C silencing inhibits HCC cell proliferation, migration and invasion, promotes apoptosis, and keeps the cell cycle in G2 phase. In addition, KIF2C silencing enhanced the sensitivity of HCC cells to cisplatin. KIF2C silencing down-regulates the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mitogen-activated protein kinase 3 (MAPK3) proteins. In conclusion, KIF2C silencing amplifies the sensitivity of HCC cells to cisplatin by regulating the PI3K/AKT/MAPK signaling pathway. Consequently, targeting KIF2C shows great application potential as a strategy for enhancing the effectiveness of HCC treatment.

Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis.

Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.

Structure-based virtual screening and molecular docking approaches to identify potential inhibitors against KIF2C to combat glioma

Glioma, a kind of malignant brain tumor, is extremely lethal. Kinesin family member 2C (KIF2C) was found to have an aberrant expression in several cancer types, including lung cancer and glioma. KIF2C may therefore be a useful therapeutic target for the treatment of glioma. In the current study, new drug candidates that may function as KIF2C enzyme inhibitors were discovered. MTi OpenScreen was used to carry out the structure-based virtual screening of an inbuilt drug library containing 150,000 compounds. These compounds belong to different classes, such as natural product-based compounds (NP-lib), purchasable approved drugs (Drugs-lib), and food constituents compound collection (FOOD-lib). Based on their binding affinities, a total of 84 compounds were further pushed to calculate ADMET properties. The compounds (16) meeting the ADMET cutoff ranges were then further docked to the receptor to find their plausible binding modes using the Glide tool’s standard precision (SP) technique. The docking results were examined using the Glide gscore, and the best binding compounds (Rimacalib and Sarizotan) were chosen to test their stability with KIF2C protein through molecular dynamics (MD) simulation. Similarly, Principal Component Analysis and cross-correlation matrix were also examined. The MM/GBSA binding free energies showed a considerable energy contribution in the binding of hits with the KIF2C. Collectively, these findings strongly suggest the potential of the lead compounds to inhibit the biological function of KIF2C, emphasizing the need for further investigation in this area. Communicated by Ramaswamy H. Sarma

KIF2C promotes clear cell renal cell carcinoma progression via activating JAK2/STAT3 signaling pathway

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors that can be highly aggressive. Despite advances in the exploration of its underlying molecular biology, the clinical outcome for advanced ccRCC is still unsatisfied. Recently, more attention was paid to the functions of Kinesin family member 2C (KIF2C) in cancer progression, while the specific function of KIF2C in ccRCC has not been sufficiently elucidated. The present study aims to investigate the role of KIF2C in the progression of ccRCC and reveal potential mechanisms. MethodsExpression of KIF2C in ccRCC tissues and adjacent normal tissue was compared and the association of KIF2C expression level with tumor grade, stage, and metastasis were analyzed using online web tool. Kaplan-Meier survival was performed to detect the association of KIF2C expression and patient’ prognosis. Stably cell lines with KIF2C knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and transwell invasion assays were carried out to explore the effect of KIF2C knockdown or overexpression on the proliferation, migration, and invasion of ccRCC cells. Gene set enrichment analysis (GSEA) was conducted to reveal signaling pathways associated with KIF2C expression. The effect of KIF2C on JAK2/STAT3 signaling pathway were explored by western blot assay. ResultsKIF2C expression was significantly upregulated in ccRCC tissues and was higher with the increase of tumor grade, stage, and metastasis. Higher expression of KIF2C was correlated with worse overall survival and diseases free survival in ccRCC patients. Silence of KIF2C inhibited proliferation, migration, and invasion in ccRCC cells. Conversely, overexpression of KIF2C had the opposite effect. GSEA results showed that JAK/STAT signaling pathway was markedly enriched in KIF2Chigh group. Pearson’ correlation revealed that KIF2C expression was significantly associated with genes in JAK2/STAT3 signaling. Western blot results showed that KIF2C knockdown decreased protein expression of p-JAK2 and p-STAT3, and KIF2C overexpression increased the phosphorylation of JAK2 and STAT3. AG490, a JAK2/STAT3 signaling inhibitor, could partly impair the tumor-promoting effects of KIF2C in ccRCC. ConclusionKIF2C expression was significantly upregulated in ccRCC and correlated with tumor grade, stage, metastasis, and patients’ prognosis. KIF2C promoted ccRCC progression via activating JAK2/STAT3 signaling pathway, and KIF2C might be a novel target in ccRCC therapy.

Bioinformatical analysis of the key differentially expressed genes for screening potential biomarkers in Wilms tumor

Wilms tumor (WT) is the most common pediatric renal malignant tumor in the world. Overall, the prognosis of Wilms tumor is very good. However, the prognosis of patients with anaplastic tumor histology or disease relapse is still poor, and their recurrence rate, metastasis rate and mortality are significantly increased compared with others. Currently, the combination of histopathological examination and molecular biology is essential to predict prognosis and guide the treatment. However, the molecular mechanism has not been well studied. Genetic profiling may be helpful in some way. Hence, we sought to identify novel promising biomarkers of WT by integrating bioinformatics analysis and to identify genes associated with the pathogenesis of WT. In the presented study, the NCBI Gene Expression Omnibus was used to download two datasets of gene expression profiles related to WT patients for the purpose of detecting overlapped differentially expressed genes (DEGs). The DEGs were then uploaded to DAVID database for enrichment analysis. In addition, the functional interactions between proteins were evaluated by simulating the protein–protein interaction (PPI) network of DEGs. The impact of selected hub genes on survival in WT patients was analyzed by using the online tool R2: Genomics Analysis and Visualization Platform. The correlation between gene expression and the degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA. Top 12 genes were identified for further study after constructing a PPI network and screening hub gene modules. Kinesin family member 2C (KIF2C) was identified as the most significant gene predicting the overall survival of WT patients. The expression of KIF2C in WT was further verified by quantitative real-time polymerase chain reaction and immunohistochemistry. Furthermore, we found that KIF2C was significantly correlated with immune cell infiltration in WT. Our present study demonstrated that altered expression of KIF2C may be involved in WT and serve as a potential prognostic biomarker for WT patients.

Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity.

Adverse cardiovascular events are associated with vascular calcification (VC) process, where vascular smooth muscle cells (VSMCs) differentiate into osteoblastic phenotype and deposit hydroxyapatite crystals. Microtubule-associated protein kinesin family member 2C (KIF2C) expression is decreased obviously in VSMC during calcification induction. Accordingly, we investigate the role and potential mechanism of KIF2C on VSMC calcification. The effects of β-glycerophosphate (β-GP)/KIF2C/lumican (LUM) on calcification, calcium content, alkaline phosphatase (ALP) activity, calcification-related markers, Tubulin, the ratio of polymerized (Po) to free (Fr) tubulin, as well as levels of LUM, apolipoprotein B (APOB), and KIF2C were assessed by Alizarin red S staining, calcium assay kit, ALP assay kit, Western blot, immunofluorescence, and quantitative real-time PCR. The interplay between LUM and APOB was estimated using co-immunoprecipitation and immunofluorescence. As a result, β-GP promoted calcification of human VMSCs (HVMSCs) and repressed KIF2C expression. KIF2C overexpression reversed the effect of β-GP on HVSMCs. LUM silencing attenuated β-GP-induced promotion on HVSMC calcification and increased KIF2C expression by interacting with APOB. Collectively, LUM silencing can alleviate β-GP-induced VSMC calcification through mitigating the repression of APOB on KIF2C expression.

Knockdown of kinesin family member 2C restricts cell proliferation and induces cell cycle arrest in gastric cancer.

Kinesin family member 2C (KIF2C) was reported to act as a vital player in several human cancers. However, the exact function of KIF2C in gastric cancer (GC) is poorly understood. In the present study, the potential role of KIF2C was studied in gastric cancer by bioinformatics analysis and proliferation assay. KIF2C expression was detected using reverse transcription-quantitative polymerase chain reaction and western blot. Our data showed that the expression of KIF2C was increased in different tumor tissues, including GC. KIF2C was overexpressed in GC tissues and might be used as a diagnostic and prognostic biomarker for GC. KIF2C expression was correlated with immune infiltration and the levels of cell cycle-related genes in GC. Moreover, silencing of KIF2C can cause cell cycle arrest, and inhibit the proliferative ability of GC cells. Thus, our studies revealed that KIF2C levels might serve as a promising biomarker for diagnosis and prediction of prognosis of GC, and targeting KIF2C might be an effective therapeutic strategy for GC.

Ablation of KIF2C in Purkinje cells impairs metabotropic glutamate receptor trafficking and motor coordination in male mice.

Kinesin family member 2C (KIF2C)/mitotic centromere-associated kinesin (MCAK), is thought to be oncogenic as it is involved in tumour progression and metastasis. Moreover, it also plays a part in neurodegenerative conditions like Alzheimer's disease and psychiatric disorders such as suicidal schizophrenia. Our previous study conducted on mice demonstrated that KIF2C is widely distributed in various regions of the brain, and is localized in synaptic spines. Additionally, it regulates microtubule dynamic properties through its own microtubule depolymerization activity, thereby affecting AMPA receptor transport and cognitive behaviour in mice. In this study, we show that KIF2C regulates the transport of mGlu1 receptors in Purkinje cells by binding to Rab8. KIF2C deficiency in Purkinje cells results in abnormal gait, reduced balance ability and motor incoordination in male mice. These data suggest that KIF2C is essential for maintaining normal transport and synaptic function of mGlu1 and motor coordination in mice. KEY POINTS: KIF2C is localized in synaptic spines of hippocampus neurons, and regulates excitatory transmission, synaptic plasticity and cognitive behaviour. KIF2C is extensively expressed in the cerebellum, and we investigated its functions in development and synaptic transmission of cerebellar Purkinje cells. KIF2C deficiency in Purkinje cells alters the expression of metabotropic glutamate receptor 1 (mGlu1) and the AMPA receptor GluA2 subunit at Purkinje cell synapses, and changes excitatory synaptic transmission, but not inhibitory transmission. KIF2C regulates the transport of mGlu1 receptors in Purkinje cells by binding to Rab8. KIF2C deficiency in Purkinje cells affects motor coordination, but not social behaviour in male mice.

KIF2C accelerates the development of non-small cell lung cancer and is suppressed by miR-186-3p via the AKT-GSK3β-β-catenin pathway

This study aimed to explore how kinesin family member 2C (KIF2C) influences the progression of non-small cell lung cancer (NSCLC). The levels of KIF2C and microRNA-186-3p (miR-186-3p) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Through the utilization of cell counting kit-8 (CCK-8) assay, colony formation assay, wound closure assay, and Transwell assay, NSCLC cell proliferation, migration, and invasion were identified, respectively. NSCLC cell apoptosis was assessed using the TUNEL assay and flow cytometry (FCM) assay. Luciferase reporter analysis was used to investigate the relationship between KIF2C and miR-186-3p. Western blot assays were conducted to investigate the influence of KIF2C on the AKT-GSK3β-β-catenin pathway. The results showed that KIF2C was up‐regulated in NSCLC cells, which predicted poor prognosis. KIF2C overexpression promoted the proliferation, migration, and invasion of NSCLC cells as well as inhibited NSCLC cell apoptosis. KIF2C was as a key target of miR-186-3p. High expression of KIF2C, meanwhile, increased the levels of β-catenin, p-GSK-3β and phosphorylated protein kinase B (p-AKT). KIF2C downregulation and miR-186-3p upregulation reversed these outcomes. As an oncogenic factor, KIF2C is negatively regulated by miR-186-3p and participates in the progression of NSCLC through the AKT-GSK3β-β-catenin pathway.

KIF2C Facilitates Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a poor prognosis. For PDAC, an increase in the survival time of patients and a reduction mortality have not yet successfully been achieved. In many research works, Kinesin family member 2C (KIF2C) is highly expressed in several tumors. Nevertheless, the role of KIF2C in pancreatic cancer is unknown. In this study, we found that KIF2C expression is significantly upregulated in human PDAC tissues and cell lines such as ASPC-1 and MIA-PaCa2. Moreover, KIF2C upregulation is associated with a poor prognosis when combining the expression of KIF2C with clinical information. Through cell functional assays and the construction of animal models, we showed that KIF2C promotes PDAC cell proliferation, migration, invasion, and metastasis, both in vitro and in vivo. Finally, the results of sequencing showed that the overexpression of KIF2C causes a decrease in some proinflammatory factors and chemokines. The cell cycle detection indicated that the pancreatic cancer cells in the overexpressed group had abnormal proliferation in the G2 and S phases. These results revealed the potential of KIF2C as a therapeutic target for the treatment of PDAC.

Identification of biomarkers related to tumorigenesis and prognosis in breast cancer.

BackgroundThe aim of the present study was to identify the central genes and prognostic index of breast cancer, and to determine the relationship between prognostic index and immune infiltration levels to provide useful information for the diagnosis and treatment of breast cancer.MethodsThe Cancer Genome Atlas breast cancer dataset and 2 microarray datasets were applied to screen overlapping differentially expressed genes (DEGs) between breast cancer tissue and normal breast tissue samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted through the Database for Annotation, Visualization, and Integrated Discovery. Protein-protein interaction (PPI) networks were used to screen hub genes of the overlapping DEGs. Gene Expression Profiling Interactive Analysis (GEPIA), The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and The Human Protein Atlas (HPA) databases were used to validate their expression. The correlation of hub genes with immune infiltration was analyzed using TISIDB software. Kaplan-Meier Plotter was used to analyze the prognosis of hub genes.ResultsTen hub genes [cyclin A2 (CCNA2), cyclin dependent kinase 1 (CDK1), centromere protein F (CENPF), kinesin family member 2C (KIF2C), kinesin family member 4A (KIF4A), maternal embryonic leucine zipper kinase (MELK), PDZ binding kinase (PBK), protein regulator of cytokinesis 1 (PRC1), DNA topoisomerase II alpha (TOP2A), and TPX2 microtubule nucleation factor (TPX2)] were selected and their overexpression in breast cancer tissue was verified. All were associated with a poor prognosis for breast cancer. CDK1, CENPF, KIF2C, KIF4A, MELK, PBK, PRC1, and TPX2 were correlated with CD4 T cells in breast cancer, while TOP2A was correlated with CD8 T cells.ConclusionsThe findings indicated that the 10 hub genes could be potential biomarkers for progression in breast cancer.

Comprehensive analysis of the effects of KIF2C on prognosis, biological functions and immune infiltration in PAAD

Kinesin family member 2 C (KIF2C), a modulator of microtubule depolymerization, bipolar spindle formation, and chromosome segregation, has been reported to play roles in cancer biology. Moreover, many articles have reported that KIF2C expression is closely associated with the progression and prognosis of a variety of tumors. However, the role of KIF2C in pancreatic cancer is unclear. In this study, we used various databases to investigate the correlation between KIF2C expression and pancreatic cancer. MethodsFirst, we determined the location of KIF2C in tumour cell lines via The Human Protein Atlas and immunofluorescence staining. Then, we analysed the GEPIA2 and TISIDB databases to assess KIF2C expression in pancreatic cancer cells and its correlation with the prognosis of pancreatic cancer. Through the Linkdeomics database, we identified the mRNAs whose expression was correlated with KIF2C expression. Next, we used the miRDB, miRanda, miRTairBase, Targetscan and miRmap databases to predict miRNAs that interact with KIF2C. Furthermore, we performed PPI analysis of KIF2C using the STRING database and Cytoscape Mcode software. The TISIDB database was used to analyse the correlation between KIF2C expression and immunity in pancreatic cancer. Finally, datasets GSE62452 and PACA-UA(https://xenabrowser.net/datapages/?cohort=PACA-AU&removeHub=http%3 A%2 F%2F127.0.0.1%3A7222) were used to validate the results of survival analysis and immune analysis. ResultsIt was revealed that KIF2C was mainly located in the nuclei of pancreatic cancer cells. We found that the KIF2C mRNA expression levels in pancreatic cancer tissues were higher than those in normal tissues. Notably, elevated KIF2C mRNA expression was significantly associated with decreased overall survival and disease-free survival in patients with pancreatic cancer. Furthermore, KIF2C expression was closely related to the expression of multiple proteins and miRNAs in pancreatic cancer tissues. In addition, KIF2C expression was closely related to CD4+T cells. These results indicated that the expression of KIF2C was closely related to the prognosis of pancreatic cancer. ConclusionKIF2C expression is negatively correlated with the prognosis of pancreatic cancer patients, and one of the main mechanisms underlying this relationship may be related to the tumor immune microenvironment.

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent cancers of the urinary system. In previous research, Kinesin family member 2C (KIF2C), as an oncogene, has been demonstrated to have a key role in the incidence and progression of different cancers. However, KIF2C has not been reported in PCa. We combined data from different databases, including The Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and the Genomics of Drug Sensitivity in Cancer database, to explore the potential oncogenic role of KIF2C in PCa through a series of bioinformatics approaches, including analysis of the association between KIF2C and prognosis, clinicopathological features, gene mutations, DNA methylation, immune cell infiltration, and drug resistance. The results showed that KIF2C was significantly up-regulated in PCa. High KIF2C expression was associated with age, pathological stage, lymph node metastases, prostate-specific antigen (PSA), and Gleason score and significantly predicted an unfavorable prognosis in PCa patients. Results from Gene Set Enrichment Analysis (GSEA) suggested that KIF2C was involved in the cell cycle and immune response. KIF2C DNA methylation was reduced in PCa and was inversely linked with KIF2C expression. KIF2C was shown to have a strong relationship with the tumor microenvironment (TME), infiltrating cells, and immune checkpoint genes. Furthermore, high KIF2C expression was significantly resistant to a variety of MAPK signaling pathway-related inhibitors. Our study reveals that KIF2C may be a possible predictive biomarker for assessing prognosis in PCa patients with immune infiltration.

Identification of hub genes associated with bladder cancer using bioinformatic analyses.

BackgroundBladder cancer (BLCA) is the ninth most common cancer worldwide, with high mortality and recurrence rates. Studies have increasingly reported that molecular diagnosis contributes to the early diagnosis and prognostic assessment of diseases. Thus, this study aims to find new biomarkers for the diagnosis and prognosis of BLCA.MethodsThe microarray datasets GSE147983 and The Cancer Genome Atlas (TCGA)-BLCA mRNA were obtained from the Gene Expression Omnibus (GEO) and TCGA. Differentially expressed genes (DEGs) were screened using the R “Limma” package. The “ClusterProfiler” package was used to conduct Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs. A DEG protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. The functional module was reanalyzed using Cytoscape’s Molecular Complex Detection (“MCODE”) plugin, and key genes related to BLCA were identified via the “cytoHubba” plugin. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the Tumor Immune Estimation Resource (TIMER) were used to verify the correlation between hub gene expression and immunity. A survival analysis of hub genes was performed using the Kaplan–Meier Plotter online tool.ResultsA total of 355 DEGs were screened out, including 236 upregulated and 119 downregulated DEGs. Some of the GO terms and pathways, such as chromosome separation, cell cycle, and cell senescence, were found to be significantly enriched in the DEGs. The key genes were kinesin family member 11 (KIF11), DLG associated protein 5 (DLGAP5), non-SMC condensin I complex subunit G (NCAPG), cell division cycle 20 (CDC20), cyclin B2 (CCNB2), BUB1 mitotic checkpoint serine (BUB1B), TPX2 microtubule nucleation factor (TPX2), NUF2 component of NDC80 kinetochore complex (NUF2), kinesin family member 2C (KIF2C), and cyclin B1 (CCNB1). Nine of them were immune-related, including KIF11, DLGAP5, NCAPG, CDC20, CCNB2, BUB1B, NUF2, KIF2C, and CCNB1. Survival analysis showed that the overexpression of BUB1B, CCNB1, CDC20, and DLGAP5 significantly reduced overall survival (OS) in patients with BLCA.ConclusionsThis study provided a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of BLCA by screening potential biomarkers of BLCA.

Identification of Alternative Splicing Events Associated with Paratuberculosis in Dairy Cattle Using Multi-Tissue RNA Sequencing Data.

Paratuberculosis is a major endemic disease caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection and leads to huge economic loss in the dairy sector worldwide. Alternative splicing (AS) events, playing indispensable regulatory roles in many protein functions and biological pathways, are shown to be associated with complex traits and diseases. In this study, by integrating the RNA sequencing (RNA-seq) data of 24 samples from three tissues (peripheral blood, jejunum and salivary gland) of Holstein cows, we obtained 2,706,541,696 uniquely mapped reads in total that represented 12,870 expressed genes, and detected 4285 differentially expressed genes (DEGs) between MAP-infected and healthy cows (p < 0.05). Of them, 92 differentially expressed splicing factors (DESFs) were included. Further, 119, 150 and 68 differential alternative splicing (DAS) events between MAP-infected and healthy cows were identified in peripheral blood, jejunum and salivary glands, respectively. Of note, six DAS events were highly and significantly correlated with the DESFs (R2 > 0.9; p < 0.01), and their corresponding genes (COPI coat complex subunit gamma 2 gene (COPG2), kinesin family member 2C gene (KIF2C), exocyst complex component 7 (EXOC7), Rab9 effector protein with kelch motifs gene (RABEPK), deoxyribonuclease 1 gene (DNASE1) and early endosome antigen 1 gene (EEA1)) were significantly enriched in immune response such as vesicle-mediated transport, regulation of acute inflammatory response and tuberculosis through gene ontology (GO) and KEGG analysis. KS test showed that the DAS events in the EXOC7 and KIF2C genes indeed displayed differences between MAP-infected cows and healthy cows. The DAS in EXOC7 might produce a new protein sequence with lack of 23 amino acids, and the DAS in KIF2C induced a stop codon of premature occurrence and resulted in a lack of functional domain. In summary, this study identified the DAS events and corresponding genes related to MAP-infection base on the RNA-seq data from multiple tissues of Holstein cows, providing novel insights into the regulatory mechanisms underpinning paratuberculosis in dairy cattle.

Down regulated oncogene KIF2C inhibits growth, invasion, and metastasis of hepatocellular carcinoma through the Ras/MAPK signaling pathway and epithelial-to-mesenchymal transition.

BackgroundHepatocellular carcinoma (HCC) is the leading cause of cancer death. Kinesin family member 2C (KIF2C) has been shown as oncogene in a variety of tumors. However, its role in HCC remains unclear.MethodsIn this study, the expression level of KIF2C in HCC was detected by immunohistochemical staining and RT-PCR, and verified by Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine database. A curve was established to evaluate the diagnostic efficiency of KIF2C. The effect of KIF2C on HCC was investigated by flow cytometry, Cell Counting Kit-8, Transwell, and the wound-healing assay. We explored the underlying mechanism through epithelial-to-mesenchymal transition (EMT) and transcriptome sequences analysis.ResultsKIF2C was overexpression in HCC tissue and related to neoplasm histologic grade (P<0.001), pathology stage (P=0.001), and a dismal prognosis (overall, recurrence-free, and disease-free survival). The diagnostic efficacy of KIF2C was >90% in diagnosing HCC. The HCC cell function experiments showed that KIF2C promoted HCC cell proliferation, migration, invasion, and an accelerated cell cycle, and inhibited apoptosis. Based on western blot analysis and RT-PCR, we found that KIF2C promoted HCC invasion and metastasis through activation of the EMT. Based on transcriptome sequences, we showed that KIF2C promoted HCC through the Ras/MAPK and PI3K/Akt signaling pathway.ConclusionsKIF2C was found to promote the progression of HCC and is anticipated to serve as a biomarker for HCC diagnosis, prognosis, and targeted therapy.

Characterization of Kinesin Family Member 2C as a Proto-Oncogene in Cervical Cancer.

Kinesin family member 2C (KIF2C) is known as an oncogenic gene to regulate tumor progression and metastasis. However, its pan-cancer analysis has not been reported. In this study, we comprehensively analyzed the characteristics of KIF2C in various cancers. We found that KIF2C was highly expressed and corresponded to a poor prognosis in various cancers. We also found a significant correlation between KIF2C and clinicopathological characteristics, particularly in cervical cancer, which is the most common gynecological malignancy and is the second leading cause of cancer-related deaths among women worldwide. KIF2C mutation is strongly associated with the survival rate of cervical cancer, and KIF2C expression was significantly upregulated in cervical cancer tissues and cervical cancer cells. Moreover, KIF2C promoted cervical cancer cells proliferation, invasion, and migration in vitro and as well increased tumor growth in vivo. KIF2C knockdown promotes the activation of the p53 signaling pathway by regulating the expression of related proteins. The rescue assay with KIF2C and p53 double knockdown partially reversed the inhibitory influence of KIF2C silencing on cervical cancer processes. In summary, our study provided a relatively comprehensive description of KIF2C as an oncogenic gene and suggested KIF2C as a therapeutic target for cervical cancer.