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Backgrounds: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation. Research on KIF2C may be a new direction and target for anti-tumor therapy. Object: The article aims at reviewing current literatures and summarizing the research status of KIF2C in malignant tumors as well as the oncogenic signaling pathways associated with KIF2C and its role in immune infiltration. Result: In this review, we summarize the KIF2C mechanisms and signaling pathways in different malignant tumors, and briefly describe its involvement in pathways related to classical chemotherapeutic drug resistance, such as MEK/ERK, mTOR, Wnt/β-catenin, P53 and TGF-β1/Smad pathways. KIF2C upregulation was shown to promote tumor cell migration, invasion, chemotherapy resistance and inhibit DNA damage repair. It was also highly correlated with microRNAs, and CD4 +T cell and CD8 +T cell tumor immune infiltration. Conclusion: This review shows that KIF2C may function as a new anticancer drug target with great potential for malignant tumor treatment and the mitigation of chemotherapy resistance.

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.

Abstract Background The kinesin-13 family member 2C (KIF2C) is a versatile protein participating in many biological processes. KIF2C is frequently up-regulated in multiple types of cancer and is associated with cancer development. However, the role of KIF2C in immune cell infiltration of tumor microenvironment and immunotherapy in breast cancer remains unclear. Methods The expression of KIF2C was analyzed using Tumor Immune Estimation Resource (TIMER) database and further verified by immunohistochemical staining in human breast cancer tissues. The correlation between KIF2C expression and clinical parameters, the impact of KIF2C on clinical prognosis and independent prognostic factors were analyzed by using TCGA database, the Kaplan-Meier plotter, and Univariate and multivariate Cox analyses, respectively. The nomograms were constructed according to independent prognostic factors and validated with C-index, calibration curves, ROC curves, and decision curve analysis. A gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms of KIF2C. 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 (ssGSEA). The Tumor mutational burden and Tumor Immune Dysfunction and Rejection (TIDE) were used to analyze immunotherapeutic efficiency. Finally, the KIF2C-related competing endogenous RNA (ceRNA) network was constructed to predict the putative regulatory mechanisms of KIF2C. Results KIF2C was remarkably up-regulated in 18 different types of cancers, including breast cancer. Kaplan-Meier survival analysis showed that high KIF2C expression was associated with poor overall survival (OS). KIF2C expression was associated with clinical parameters such as age, TMN stage, T status, and molecular subtypes. We identified age, stage, estrogen receptor (ER) and KIF2C expression as OS-related independent prognosis factors for breast cancer. An OS-related nomogram was developed based on these independent prognosis factors and displayed good predicting ability for OS of breast cancer patients. Finally, our results revealed that KIF2C was significantly related to immune cell infiltration, tumor mutational burden, and immunotherapy in patients with breast cancer. Conclusion KIF2C was overexpressed in breast cancer and was positively correlated with immune cell infiltration and immunotherapy response. Therefore, KIF2C can serve as a potential biomarker for prognosis and immunotherapy in breast cancer.

Background: Clear 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. Methods: Expression 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. Results: KIF2C 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. Conclusion: KIF2C 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.

Abstract Unlike normal cells, cancer cells frequently exhibit supernumerary centrosomes, leading to formation of multipolar spindles that can trigger cell death. Nevertheless, cancer cells with supernumerary centrosomes escape the deadly consequences of unequal segregation of genomic material by coalescing their centrosomes into two poles. This unique trait of cancer cells presents a promising target for cancer therapy, focusing on selectively attacking cells with supernumerary centrosomes. Nek2A is a kinase involved in mitotic regulation, including the centrosome cycle, where it phosphorylates linker proteins to separate centrosomes. In this study, we investigated if Nek2A also prevents clustering of supernumerary centrosomes, akin to its separation function. Reduction of Nek2A activity, achieved through knockout, silencing, or inhibition, promotes centrosome clustering, whereas its overexpression results in inhibition of clustering. Significantly, prevention of centrosome clustering induces cell death, but only in cancer cells with supernumerary centrosomes, both in vitro and in vivo. Notably, none of the known centrosomal (e.g., CNAP1, Rootletin, Gas2L1) or non-centrosomal (e.g., TRF1, HEC1) Nek2A targets were implicated in this machinery. Additionally, Nek2A operated via a pathway distinct from other proteins involved in centrosome clustering mechanisms, like HSET and NuMA. Through TurboID proximity labeling analysis, we identified novel proteins associated with the centrosome or microtubules, expanding the known interaction partners of Nek2A. KIF2C, in particular, emerged as a novel interactor, confirmed through coimmunoprecipitation and localization analysis. The silencing of KIF2C diminished the impact of Nek2A on centrosome clustering and rescued cell viability. Additionally, elevated Nek2A levels were indicative of better patient outcomes, specifically in those predicted to have excess centrosomes. Therefore, while Nek2A is a proposed target, its use must be specifically adapted to the broader cellular context, especially considering centrosome amplification. Discovering partners such as KIF2C offers fresh insights into cancer biology and new possibilities for targeted treatment.

Objective: To explore the effects of kinesin-13 family member 2C (KIF2C) on hepatocellular carcinoma (HCC) cell proliferation, invasion and migration as well as human umbilical vein endothelial cell (HUVEC) angiogenesis to provide potential targets for HCC treatment. Methods: Database data were used to analyze the expression of KIF2C mRNA and protein in HCC tissues and its correlation with the expression of angiogenesis-associated factors (VEGFR2 and HIF-1α). Human normal hepatocytes QSG-7701, HUVEC, and HCC cells Huh-7 and Hep3B2.1-7 were routinely cultured, and sh-NC and sh KIF2C were transfected into Huh-7 and Hep3B2.1-7 cells with Lipofectamine 3000 transfection reagent. qPCR was performed to detect the expression of KIF2C mRNA in QSG-7701, Huh-7 and Hep3B2.1-7 cells of each group, and WB was performed to detect the expression of KIF2C protein in cells of each group, and the effect of KIF2C knockdown on the clone formation of Huh3B2.1-7 and Huh-7 cells was examined in the clonogenic assay. Tubulogenesis assay to detect the effect of conditioned cultures of knockdown KIF2C-expressing Huh-7 and Hep3B2.1-7 cells on the angiogenic capacity of HUVEC cells. Results: Database analysis showed that KIF2C mRNA and protein were highly expressed in HCC tissues (both P<0.01). In addition, database analysis suggested that KIF2C mRNA may also be highly expressed in HCC cells, and the results of KIF2C mRNA and protein expression detected by qPCR and WB showed that its mRNA and protein were highly expressed in HCC cells (both P<0.01), consistent with the database data analysis. Database data analysis also showed that KIF2C was positively correlated with the expression levels of VEGFR2 and HIF-1α in HCC tissues (P<0.05 or P<0.01). Stable low KIF2C-expressing Huh-7 and Hep3B2.1-7 cells were successfully constructed (both P<0.01), and knockdown of KIF2C expression significantly inhibited the proliferative (all P<0.01), invasive and migratory (all P<0.01) capacities of Huh-7 and Hep3B2.1-7 cells, and the conditioned culture medium of HCC cells with knockdown of KIF2C expression could significantly inhibit the angiogenic capacity of HUVEC cells in vitro (P<0.05 or P<0.01). Conclusion: KIF2C promotes the ability of Huh-7 and Hep3B2.1-7 cells to proliferate, invade and migrate as well as HUVEC angiogenesis, suggesting that KIF2C may be a potential target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Klinefelter syndrome (KS) is a leading contributor to male infertility and is characterised by complex and diverse clinical features; however, genetic changes in the KS transcriptome remain largely unknown. We therefore used transcriptomic and single‐cell RNA sequencing (scRNA‐seq) datasets from KS versus normal populations through the Gene Expression Omnibus (GEO) database to identify gene biomarkers associated with the occurrence of KS. We identified a total of 700 differentially expressed genes (DEGs) and completed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), enrichment pathway analysis and protein‐protein interaction (PPI) network analysis. A total of four unreported KS‐related hub genes (KIF2C, MRPS2, RPS15 and TSFM) were identified. Validation of the single‐cell sequencing dataset showed that only KIF2C and RPS15 were expressed in spermatocytes and that they were differentially expressed in sperm cells. Further construction of the developmental trajectories of these two genes in sperm cells showed that the KIF2C gene showed an upward trend throughout the differentiation and development of sperm cells. In conclusion, we report here that KIF2C may be closely related to the differentiation and development of sperm cells in KS patients, which is important for revealing the molecular mechanism of KS and conducting further studies.

Abstract 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.

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of mortality, while the underlying mechanism remains unclear. Our studies have revealed that KIF2C plays a crucial role in tumor proliferation and metastasis in HNSCC. The results demonstrate that KIF2C is highly expressed at both the mRNA and protein levels and is closely associated with lymph node metastasis. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicate that the differentially expressed genes are enriched in processes or pathways related to cell adhesion and cell mitosis in HNSCC. Moreover, the established protein-protein interaction network identifies KIF2C as a potential hub gene in HNSCC. Knockdown of KIF2C has been demonstrated to significantly reduce cell migration and invasion ability, leading to cell cycle arrest, a high proportion of abnormal cell apoptosis, and cell chromosome division mismatches in the HNSCC cell line. Downstream genes such as PDGFA, EGFR, TP63, SNAI2, KRT5, and KRT14 were found to be down-regulated, and multiple critical pathways, including mTOR, ERK, and PI3K-AKT pathways, were inactivated as a result of KIF2C knockdown. These findings provide strong evidence for the crucial role of KIF2C in HNSCC and suggest that targeting KIF2C may be a promising therapeutic strategy for this disease. Knockdown of KIF2C has been shown to significantly inhibit tumor proliferation in nude mice, demonstrating the potential therapeutic role of KIF2C in HNSCC treatment., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Skin Cutaneous Melanoma (SKCM) is known as an aggressive malignant cancer, which could be directly derived from melanocytic nevi. However, the molecular mechanisms underlying the malignant transformation of melanocytes and melanoma tumor progression still remain unclear. Increasing research showed significant roles of epigenetic modifications, especially DNA methylation, in melanoma. This study focused on the identification and analysis of methylation-regulated differentially expressed genes (MeDEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles.Methods: The gene expression profiling datasets (GSE3189 and GSE114445) and gene methylation profiling datasets (GSE86355 and GSE120878) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified via GEO2R. MeDEGs were obtained by integrating the DEGs and DMGs. Then, a functional enrichment analysis of MeDEGs was performed. STRING and Cytoscape were used to describe the protein-protein interaction (PPI) network. Furthermore, survival analysis was implemented to select the prognostic hub genes. Next, we conducted gene set enrichment analysis (GSEA) of hub genes. To validate, SKCM cell culture and lentivirus infection was performed to reveal the expression and behavior pattern of KIF2C. Patients and specimens were collected and then immunohistochemistry (IHC) staining was conducted.Results: We identified 237 hypomethylated, upregulated genes and 182 hypermethylated, downregulated genes. Hypomethylation-upregulated genes were enriched in biological processes of the oxidation-reduction process, cell proliferation, cell division, phosphorylation, extracellular matrix disassembly and protein sumoylation. Pathway enrichment showed selenocompound metabolism, small cell lung cancer and lysosome. Hypermethylation-downregulated genes were enriched in biological processes of positive regulation of transcription from RNA polymerase II promoter, cell adhesion, cell proliferation, positive regulation of transcription, DNA-templated and angiogenesis. The most significantly enriched pathways involved the transcriptional misregulation in cancer, circadian rhythm, tight junction, protein digestion and absorption and Hippo signaling pathway. After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL. Moreover, the most involved hallmarks obtained by GSEA were E2F targets, G2M checkpoint and mitotic spindle. Importantly, among the 7 hub genes, we found that down-regulated level of KIF2C expression significantly inhibited the proliferative ability of SKCM cells and suppressed the metastasis capacity of SKCM cells.Conclusions: Our study identified potential aberrantly methylated-differentially expressed genes participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL provided clues of aberrantly methylation-based biomarkers, which might improve the development of precision medicine. KIF2C plays a pro-tumorigenic role and potentially inhibited the proliferative ability in SKCM.

Objective: To investigate the relationship between the expression of kinesin superfamily 2A (KIF2A), kinesin superfamily 2C (KIF2C), and kinesin superfamily 20A (KIF20A) messenger ribonucleic acid in non-small cell lung cancer (NSCLC) tissues and clinical pathological characteristics and prognosis. Methods: 106 patients with NSCLC who were underwent surgical resection in Tianjin medical university general hospital from September 2016 to September 2019 were selected, the cancerous tissues and its corresponding adjacent tissues were taked, the expression of KIF2A, KIF2C and KIF20A m RNA were detected in tissues by fluorescence quantitative polymerase chain reaction (RT-qPCR), and its relationship with clinical pathological characteristics was analyzed. The relationship between the expression of KIF2A, KIF2C, and KIF20A m RNA in NSCLC tissues was analyzed by Pearson correlation. 3 years followed up, the relationship between the expression of KIF2A, KIF2C, and KIF20A m RNA and patients prognosis was analyzed by the Kaplan-Meier survival curve. Results: The expression levels of KIF2A, KIF2C, and KIF20A m RNA in NSCLC cancer tissues were significantly higher than those in adjacent tissues (P＜0.05) . The expression levels of KIF2A, KIF2C, and KIF20A m RNA in poorly differentiated, lymph node metastasis, and clinical stage IIIA in NSCLC cancer tissues were significantly higher than those in medium to high differentiated, non lymph node metastasis, and clinical stage I and II in NSCLC cancer tissues (P＜0.05) . Pearson correlation analysis showed that the expres sion of KIF2A m RNA in NSCLC cancer tissues was positively correlated with the expression of KIF2C m RNA and KIF20A m RNA, and the expression of KIF2C m RNA was positively correlated with the expression of KIF20A m RNA (P＜0.05) . KaplanMeier method analysis showed that the 3 years survival rates in KIF2A m RNA low expression group, KIF2C m RNA low expression group, and KIF20A m RNA low expression group were (84.78%, 86.27%, 81.48%) significantly higher than those in KIF2A m RNA high expression group, KIF2C m RNA high expression group, and KIF20A m RNA high expression group (59.62%, 55.32%, 59.09%) (P＜0.05) .Conclusion: KIF2A, KIF2C, and KIF20A m RNA are high expression in NSCLC tissues, and which are related to poorly differentiated, lymph node metastasis, clinical stage and prognosis. [ABSTRACT FROM AUTHOR]

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.

Kinesin superfamily member 2C (KIF2C) is an essential regulator of the cell cycle and its aberrant expression can promote tumor progression. However, the mechanism of KIF2C in pan-cancer is unclear.Data were obtained from public databases, including The Cancer Genome Atlas (TCGA), UALCAN, TIMER and CellMiner. The data came from public databases such as The Cancer Genome Atlas (TCGA), UALCAN, TIMER, and CellMiner. We analyzed the correlation of KIF2C with expression, prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repairs (MMR), immune infiltration and anticancer drug sensitivity by R language.KIF2C was highly expressed in several tumors and correlated with poor prognosis. KIF2C expression was significantly correlated with TMB, MSI, MMRs, and immune checkpoint genes, and with the level of immune cell infiltration such as tumor-associated macrophage (TAM), cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs) and Tregs. The GO and KEGG results suggest that KIF2C is involved in immune regulation in addition to cell cycle regulation.In addition, KIF2C is associated with DNA methylation, m6A modifications and m7G modifications. Our data suggest that KIF2C is a prognostic biomarker linked to immunosuppression, targeting KIF2C may improve the outcome of immunotherapy. Our findings indicate that KIF2C is a prognostic biomarker associated with immunosuppression, and that targeting KIF2C may improve the outcome of immunotherapy.

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.

Kinesin superfamily member 2C (KIF2C) is an essential regulator of the cell cycle and its aberrant expression can promote tumor progression. However, the mechanism of KIF2C in pan-cancer is unclear.Data were obtained from public databases, including The Cancer Genome Atlas (TCGA), UALCAN, TIMER and CellMiner. The data came from public databases such as The Cancer Genome Atlas (TCGA), UALCAN, TIMER, and CellMiner. We analyzed the correlation of KIF2C with expression, prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repairs (MMR), immune infiltration and anticancer drug sensitivity by R language.KIF2C was highly expressed in several tumors and correlated with poor prognosis. KIF2C expression was significantly correlated with TMB, MSI, MMRs, and immune checkpoint genes, and with the level of immune cell infiltration such as tumor-associated macrophage (TAM), cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs) and Tregs. The GO and KEGG results suggest that KIF2C is involved in immune regulation in addition to cell cycle regulation.In addition, KIF2C is associated with DNA methylation, m6A modifications and m7G modifications. Our data suggest that KIF2C is a prognostic biomarker linked to immunosuppression, targeting KIF2C may improve the outcome of immunotherapy. Our findings indicate that KIF2C is a prognostic biomarker associated with immunosuppression, and that targeting KIF2C may improve the outcome of immunotherapy. [ABSTRACT FROM AUTHOR]

Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules are the major route for cargo protein trafficking and they specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed depolymerization mechanism that regulates dynamic microtubules in synapses and dendrites is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a pivotal role in the structural and functional plasticity of synapses and regulates cognitive function in mice. Through its microtubule depolymerization capability, KIF2C regulates microtubule dynamics in dendrites, and regulates microtubule invasion of spines in neurons in a neuronal activity-dependent manner. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Collectively, our study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how activity-dependent microtubule dynamic regulates synaptic plasticity and cognition behaviors.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

DNA double strand breaks (DSBs) have detrimental effects on cell survival and genomic stability, and are related to cancer and other human diseases. In this study, we identified microtubule-depolymerizing kinesin Kif2C as a protein associated with DSB-mimicking DNA templates and known DSB repair proteins in Xenopus egg extracts and mammalian cells. The recruitment of Kif2C to DNA damage sites was dependent on both PARP and ATM activities. Kif2C knockdown or knockout led to accumulation of endogenous DNA damage, DNA damage hypersensitivity, and reduced DSB repair via both NHEJ and HR. Interestingly, Kif2C depletion, or inhibition of its microtubule depolymerase activity, reduced the mobility of DSBs, impaired the formation of DNA damage foci, and decreased the occurrence of foci fusion and resolution. Taken together, our study established Kif2C as a new player of the DNA damage response, and presented a new mechanism that governs DSB dynamics and repair.

Simple Summary: For patients with pancreatic cancer, due to the concealment of early symptoms, rapid progress, and easy metastasis, the prognosis is grim. Based on clinical specimens, we found that KIF2C is abnormally expressed in pancreatic cancer, related to the stage of the patient. Through in vivo and in vitro experiments, we confirmed that KIF2C affects the proliferation, invasion, and metastasis of pancreatic cancer. Following this, via flow cytometry, we detected that KIF2C affects the cell cycle of pancreatic cancer and verified the expression of some genes related to the underlying mechanism in the sequenced transcriptome data. 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. [ABSTRACT FROM AUTHOR]

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, calcificationrelated 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 [ABSTRACT FROM AUTHOR]

Relapse of acute lymphoblastic leukemia (ALL) is dangerous and it worsens the prognosis of patients; however, prognostic markers or therapeutic targets for ALL remain unknown. In the present study, using databases such as TARGET, GSE60926 and GSE28460, we determined that KIF2C and its binding partner, KIF18B are overexpressed in patients with relapsed ALL compared to that in patients diagnosed with ALL for the first time. As 50% of the residues are exactly the same and the signature domain of KIF2C is highly conserved between human and zebrafish, we used zebrafish embryos as a model to investigate the function of kif2c in vivo. We determined that kif2c is necessary for lymphopoiesis in zebrafish embryos. Additionally, we observed that kif2c is not related to differentiation of HSCs; however, it is important for the maintenance of HSCs as it provides survival signals to HSCs. These results imply that the ALL relapse-related gene KIF2C is linked to the survival of HSCs. In conclusion, we suggest that KIF2C can serve as a novel therapeutic target for relapsed ALL.

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., Methods: First, 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., Results: It 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., Conclusion: KIF2C 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., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)