• Glioblastoma
• Glioma
• Kinesin superfamily
• Motor proteins
• Signaling pathway

• Humans
• Glioma/metabolism
• Glioma/genetics
• Glioma/pathology
• Kinesins/metabolism
• Kinesins/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/genetics
• Brain Neoplasms/pathology
• Animals
• MicroRNAs/metabolism
• MicroRNAs/genetics

• Diagnosis
• Kinesin
• Marker
• Treatment
• cancer
• microRNA

• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Kinesins/metabolism
• Kinesins/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/metabolism
• Gene Expression Regulation, Neoplastic
• Animals
• Cell Proliferation/genetics
• Disease Progression
• Signal Transduction
• Apoptosis/genetics
• Cell Movement/genetics

• Cell death
• Cell proliferation
• Endometrial cancer
• KIF23

• Anaplastic thyroid cancer
• KIF23
• Migration
• Proliferation
• SIRT7
• Succinylation

• Humans
• Thyroid Carcinoma, Anaplastic/genetics
• Thyroid Carcinoma, Anaplastic/metabolism
• Cell Line, Tumor
• Apoptosis
• Thyroid Neoplasms/genetics
• Thyroid Neoplasms/metabolism
• Cell Proliferation/genetics
• Microtubule-Associated Proteins
• Sirtuins/genetics
• Sirtuins/pharmacology

• AURKB
• Alpha interferon
• BIRC5(Survivin)
• CDC20
• Drug combination
• FOXM1
• Gamma interferon
• Glioblastoma
• HeberFERON
• Mitotic cell cycle
• PLK1
• STAT1
• U-87MG
• p53

• Humans
• Glioblastoma/drug therapy
• Glioblastoma/genetics
• Apoptosis
• Cell Line, Tumor
• G2 Phase Cell Cycle Checkpoints
• Interferon-alpha/pharmacology
• Anaphase
• Interferon-gamma/pharmacology
• Skin Neoplasms

• KIF23
• STAT1
• biomarker
• diagnostic
• gastric cancer
• immune infiltration

• KCNQ1OT1
• KIF23
• Retinoblastoma
• miR-339-3p

• AR
• EMT
• KIF23
• Nasopharyngeal carcinoma
• Wnt/β-catenin signaling pathway

• bioinformatics analysis
• glioma
• kinesin superfamily
• prognosis
• signature

• Humans
• Kinesins/genetics
• Brain Neoplasms/genetics
• Glioma/genetics
• Prognosis
• Risk Factors

• Autophagy, endoplasmic reticulum stress
• Immune system
• PSMA2
• Proteasome
• Signal transduction

• SU-DHL-2 cell line
• diffuse large B-cell lymphoma
• ferroptosis
• propolis
• proteomics

This study aims to carry out a pan-cancer analysis of kinesin family member 23 (KIF23) and construct a predictive model for the prognosis of clear cell renal cell carcinoma (ccRCC) patients.

We evaluated the differential expression of KIF23 in pan-cancer by The Cancer Genome Atlas (TCGA) and Oncomine database. Then, the correlation between KIF23 with prognosis, clinical grade, stage, immune subtype, tumor mutation burden (TMB), microsatellite instability (MSI) and immune microenvironment was explored by TCGA, an integrated repository portal for tumor-immune system interactions (TISIDB) and cBioPortal. Subsequently, we screened out ferroptosis-related genes (FRGs) related to KIF23 and constructed a risk score model. Univariate Cox analysis was used to determine independent prognostic factors for ccRCC overall survival (OS), and a nomogram was established. Furthermore, gene set enrichment analysis (GSEA) was applied to study the biological functions and pathways of KIF23. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to evaluate the expression of KIF23.

KIF23 was highly expressed in most tumors. Further, KIF23 was strongly correlated with prognosis, clinical grade, stage, immune subtype, TMB, MSI and immune microenvironment in different tumors. We found that KIF23 was significantly associated with all aspects of ccRCC. Then, 8 FRGs were identified to construct a risk score model together with KIF23. And a prognostic nomogram prediction model of OS was established. After GSEA analysis, cell cycle, condensed chromosome and other physiological processes were screened out. Finally, qRT-PCR verified the high expression of KIF23 in ccRCC cell lines than normal kidney cell line.

KIF23 may act as a pivotal part in occurrence and progression of different tumors. In ccRCC, KIF23 can be a great prognostic biomarker, and the nomogram based on KIF23 may contribute to better treatment plans for ccRCC patients.

• clear cell renal cell carcinoma
• ferroptosis
• nomogram

• Breast cancer
• KIF23
• Wnt

• Animals
• Antineoplastic Agents/pharmacology
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Computer Simulation
• Female
• Gene Silencing
• Glycogen Synthase Kinase 3 beta/genetics
• Humans
• Mice
• Mice, Nude
• Microtubule-Associated Proteins/drug effects
• Microtubule-Associated Proteins/genetics
• Treatment Outcome
• Wnt Signaling Pathway/drug effects
• Xenograft Model Antitumor Assays
• beta Catenin/genetics

Background:Rhazya stricta has been used as a folkloric medicinal herb for treating various diseases such as diabetes, inflammatory disorders, and sore throat. Several studies have revealed the potential of this plant as an important source of phytochemicals with anticancer properties. Objective: The present study was designed to isolate a novel anticancer compound from Rhazya stricta and elucidate its mechanism of action using genomics approach. Methods:Rhazya stricta leaves extract was prepared, and several alkaloids were purified and characterized. These alkaloids were screened for their anticancer potential. One of the alkaloids, termed as isopicrinine, showed efficient cytotoxicity against MCF7 breast cancer cell line and was selected for further analysis. RNA-Seq transcription profiling was conducted to identify the affected genes and cellular pathways in MCF7 cells after treatment with isopicrinine alkaloid. Results: In vitro studies revealed that newly identified isopicrinine alkaloid possess efficient anticancer activity. Exposure of MCF7 cells with isopicrinine affected the expression of various genes involved in p53 signaling pathway. One of the crucial proapoptotic genes, significantly upregulated in MCF7 after exposure to alkaloid, was PUMA (p53 upregulated modulator of apoptosis), which is involved in p53-dependent and -independent apoptosis. Moreover, exposure of sublethal dose of isopicrinine alkaloid in breast cancer cell line led to the downregulation of survivin, which is involved in negative regulation of apoptosis. Besides, several genes involved in mitosis and cell proliferation were significantly downregulated. Conclusion: In this article, we report the determination of a new alkaloid isopicrinine from the aerial parts of Rhazya stricta with anticancer property. This compound has the potential to be developed as a drug for curing cancer.

• RNA-Seq
• Rhazya stricta
• alkaloids
• anticancer
• gene expression profile
• isopicrinine

The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA.

We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and ‘WGCNA’ package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R² ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by ‘glmnet’ package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model.

A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the ‘lightyellow’ module for NPM1 mutation, the ‘saddlebrown’ module for RUNX1 mutation, the ‘lightgreen’ module for TP53 mutation). ORA revealed that the ‘lightyellow’ module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The ‘saddlebrown’ module was enriched in immune response process. And the ‘lightgreen’ module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743–0.79).

We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

The online version contains supplementary material available at 10.1186/s12967-021-02914-2.

• Acute myeloid leukemia
• Prognostic signature
• Weighted co-expression network analysis

In glioma, kinesin family member 23 (KIF23) is up-regulated and plays a vital role in oncogenesis. However, the mechanism underlying KIF23 overexpression in malignant glioma remains to be elucidated. This study aims to find potential causes of KIF23 high expression at genome level. To clarify this issue, we obtained point mutation and copy number alterations (CNAs) of KIF23 in 319 gliomas using whole-exome sequencing. Only two glioma samples with missense mutations in KIF23 coding region were identified, while 7 patients were detected with amplification of KIF23. Additional analysis showed that KIF23 amplification was significantly associated with higher expression of KIF23. Gene ontology analysis indicated that higher copy number of KIF23 was associated TNF-α signaling pathway and mitotic cell circle checkpoint, which probably caused by subsequent upregulated expression of KIF23. Moreover, pan-cancer analysis showed that gaining of copy number was significantly associated with higher expression of KIF23, consolidating our findings in glioma. Thus, it was deduced that elevated KIF23 expression in glioma tended to be caused by DNA copy number amplification, instead of mutation.

• KIF23
• copy number alterations
• glioma
• malignancy
• mutation

Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mitotic nuclear division, ATPase activity, and Herpes simplex virus one infection. Ten hub genes from three significant modules were ascertained by Cytoscape (CytoHubba). Gene set enrichment analysis (GSEA) plots showed that transcription elongation factor complex was the most significantly enriched gene set positively correlated with the PAH group. At the same time, solute proton symporter activity was the most significantly enriched gene set positively correlated with the control group. Correlation analysis between hub genes suggested that SMC4, TOP2A, SMC2, KIF11, KIF23, ANLN, ARHGAP11A, SMC3, SMC6 and RAD50 may involve in the pathogenesis of PAH. Then, the miRNA-target genes regulation network was performed to unveil the underlying complex association among them. Finally, RNA extracted from monocrotaline (MCT)-induced Rat-PAH model lung artery tissues were to conduct quantitative real-time PCR (qRT-PCR) to validate these hub genes. In conclusion, our study offers new evidence for the underlying molecular mechanisms of PAH as well as attractive targets for diagnosis and treatment of PAH.

• Bioinformatics
• Computational biology
• Pulmonary Arterial Hypertension
• Transcriptomics

• MPM
• RNAseq
• gene signature
• malignant pleural mesothelioma
• overexpressed genes
• therapeutic targets

• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mesothelioma, Malignant/genetics
• Mesothelioma, Malignant/metabolism
• Neoplasm Proteins/biosynthesis
• Neoplasm Proteins/genetics
• Pleural Neoplasms/genetics
• Pleural Neoplasms/metabolism

• Triple-negative breast cancer
• epidermal growth factor receptor (EGFR)
• structural maintenance of chromosome protein 4 (SMC4)

Purpose: The aim of the present study was to reveal the clinicopathological significance and prognostic role of kinesin family member 23 (KIF23) in colorectal cancer (CRC) and characterize its biological function and the underlying mechanisms.

Methods: Bioinformatics analysis, immunohistochemistry, Western blot and qRT-PCR were utilized to investigate the expression of KIF23 in CRC tissues. The CCK-8 assay, wound healing assay and Matrigel assay were used to detect cell proliferation, migration and invasion in vitro. Western blot, immunofluorescence staining and cell function experiment were performed to explore the underlying mechanism.

Results: The overexpression of KIF23 was associated with T stage, N stage, M stage and TNM stage, and CRC patients with high KIF23 expression had a worse prognosis. KIF23 knockdown inhibits CRC cells proliferation, migration and invasion in vitro. The mechanism study determined that KIF23 activates the Wnt/β-catenin signaling pathway by promoting the nuclear translocation of β-catenin to regulate the malignant behavior of CRC cells.

Conclusion: These results suggest that KIF23 may act as a putative oncogene and a potential therapeutic target in CRC.

• Colorectal cancer
• KIF23
• Migration
• Proliferation
• Wnt/β-catenin

Hepatocellular carcinoma (HCC) is one of the most common human malignant tumors. The prognosis of HCC patients is still unsatisfying. In this study, we performed the integrated bioinformatics analysis to identify potential biomarkers and biological pathways in HCC.

Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE55048, GSE55758, and GSE56545) for the screening of the common differentially expressed genes (DEGs) between HCC tissues and matched non-tumor tissues. DEGs were subjected to Gene Ontology, KEGG pathway, and Reactome pathway analysis. The hub genes were identified by using protein–protein interaction (PPI) network analysis. The hub genes in HCC were further subjected to overall survival analysis of HCC patients. The hub genes were further validated by in vitro functional assays.

A total of 544 common differentially expressed genes were screened from three datasets. Gene Ontology, KEGG and Reactome analysis results showed that DEGs are significantly associated with the biological process of cell cycle, cell division, and DNA replication. PPI network analysis identified 20 hub genes from the DEGs. These hub genes except CENPE were all significantly up-regulated in the HCC tissues when compared to non-tumor tissues. The Kaplan–Meier survival analysis results showed that the high expression of the 20 hub genes was associated with shorter survival of the HCC patients. Further validation studies showed that knockdown of KIF14 and KIF23 both suppressed the proliferative potential, increased the caspase-3/-7 activity, up-regulated Bax expression, and promoted the invasive and migratory abilities in the HCC cells. In addition, knockdown of KIF14 and KIF23 enhanced chemosensitivity to cisplatin and sorafenib in the HCC cells. Finally, the high expression of KIF14 and KIF23 was associated with shorter progression-free survival, recurrence-free survival, and disease-specific survival of patients with HCC.

In conclusion, the present study performed the integrated bioinformatics analysis and showed that KIF14 and KIF23 silence attenuated cell proliferation, invasion, and migration, and promoted chemosensitivity of HCC cells. KIF14 and KIF23 may serve as potential biomarkers for predicting the worse prognosis of patients with HCC.

• KIF14
• KIF23
• differentially expressed genes
• hepatocellular carcinoma
• hub genes
• survival analysis

In recent research, high expression of kinesin family member 23 (KIF23), one of the kinesin motor proteins involved in the regulation of cytokinesis, has been shown to be related to poor prognosis in glioma and paclitaxel-resistant gastric cancer, as a results of the enhancement of proliferation, migration, and invasion. In this study, we analyzed the role of KIF23 in the progression of pancreatic ductal adenocarcinoma.

A bioinformatic method was used to analyze the KIF23 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the connection between high KIF23 expression and prognosis. We examined the expression of KIF23 using immunohistochemistry and analyzed the connection between the expression of KIF23 and clinicopathological features in pancreatic ductal adenocarcinoma patients. In addition, a colony formation assay, MTT assay, and western blot assay were performed in vitro, along with a mouse xenograft model in vivo, to analyze the effect of KIF23 on proliferation. Further, the correlation between KIF23 and CDCA8 was analyzed by TCGA and immunohistochemical data.

Bioinformatic results showed that KIF23 mRNA expression was higher in pancreatic tumor tissues than in normal pancreatic tissues and a poor prognosis has been linked to the high expression of KIF23. Immunohistochemistry revealed that KIF23 was highly expressed at the protein level and high expression of KIF23 correlated with adverse clinicopathological features. Our experimental results demonstrated that knockdown of KIF23 could inhibit the proliferation of pancreatic cells. Further, a positive correlation between KIF23 and CDCA8 expression existed, and KIF23 might promote pancreatic cancer proliferation by affecting CDCA8 expression.

Our data showed that high expression of KIF23 is associated with a poor prognosis, and KIF23 might be a potential therapeutic target for pancreatic ductal adenocarcinoma.

• Kinesin family member 23 (KIF23)
• pancreatic cancer
• prognosis
• proliferation
• therapeutic target

Kinesin super family 23 (KIF23) is a member of the KIF family, and it plays an important role in mitosis and cytokinesis. Loss of expression can cause mitotic arrest. The Oncomine database is one of the largest oncogene chip databases in the world, and is an integrated data mining platform for cancer gene information. By querying the database, differences in expression between tumor tissue and normal tissue can be determined.

To study the expression and prognostic significance of KIF23 in gastric cancer (GC).

We used immunohistochemistry to compare the expression of KIF23 in GC and normal gastric tissues. We mined the data on the expression and prognosis of KIF23 in GC using Oncomine and Kaplan–Meier plotter database.

Compared with normal gastric tissues, KIF23 expression was increased in GC tissues, and correlated with T, N, and tumor–node–metastasis stages. Survival analysis showed that patients with high expression of KIF23 had a poor overall survival. There were five studies in the Oncomine database in which expression of KIF23 was significantly higher in GC tissues than in normal gastric tissues (P < 0.05). Kaplan–Meier plotter database analysis showed that recurrence-free survival, overall survival, distant metastasis free survival, and post progression survival of patients with high expression of KIF23 were lower than those of patients with low expression. Further stratified analysis found that prognostic survival indicators worsened in patients with T2 and T3 poorly differentiated adenocarcinoma with high expression of KIF23.

KIF23 is highly expressed in GC and is associated with a poor prognosis of patients. It may be of great significance in the diagnosis, treatment, and prognostic evaluation of GC.

• Gastric cancer
• Kinesin super family 23
• Immunohistochemistry
• Oncomine
• Prognosis
• Kaplan–Meier plotter

• KIF23
• PVT1
• Prostate cancer
• miR-15a-5p

Increased expression of the kinesin family member 23 (KIF23) has been verified in gastric cancer (GC) and its upregulation contributes to cell proliferation. Even though, the role of KIF23 has not been fully elucidated in GC, and the mechanisms of KIF23 as an oncogene remain unknown. To further identify its potential role in GC, we analyzed gene expression data from GC patients in GEO and TCGA datasets. KIF23 was upregulated in GC, and increased expression of KIF23 correlated with poor prognosis. Importantly, KIF23 inhibition not only suppressed GC cell proliferation, tumorigenesis, but also migration and invasion, and arrested the cell cycle in the G2/M phase. Mechanistic investigations confirmed that KIF23 activated the Wnt/β-catenin signaling pathway by directly interacting with APC membrane recruitment 1 (Amer1). Furthermore, KIF23 exhibited competitive binding with Amer1 to block the association of Amer1 with adenomatous polyposis coli (APC), thus relocating Amer1 from the membrane and cytoplasm to the nucleus and attenuating the ability of Amer1 to negatively regulate Wnt/β-catenin signaling, resulting in activation of this signaling pathway. Collectively, our findings demonstrated that KIF23 promoted GC cell proliferation by directly interacting with Amer1 and activating the Wnt/β-catenin signaling pathway.

• Amer1
• KIF23
• Wnt/β-catenin signaling pathway
• cell growth
• gastric cancer

Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear.

GC patients’ data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan–Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients’ prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines.

The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan–Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression.

Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.

• Apoptosis
• Gastric cancer
• KIF15
• Prognosis
• Proliferation

Malignant peripheral nerve sheath tumor (MPNST) constitutes the leading cause of neurofibromatosis type 1–related mortality. MPNSTs contain highly rearranged hyperploid genomes and exhibit a high division rate and aggressiveness. We have studied in vitro whether the mitotic kinesins KIF11, KIF15, and KIF23 have a functional role in maintaining MPNST cell survival and can represent potential therapeutic vulnerabilities.

We studied the expression of kinesin mRNAs and proteins in tumors and cell lines and used several in vitro functional assays to analyze the impact of kinesin genetic suppression (KIF15, KIF23) and drug inhibition (KIF11) in MPNST cells. We also performed in vitro combined treatments targeting KIF11 together with other described MPNST targets.

The studied kinesins were overexpressed in MPNST samples. KIF15 and KIF23 were required for the survival of MPNST cell lines, which were also more sensitive than benign control fibroblasts to the KIF11 inhibitors ispinesib and ARRY-520. Co-targeting KIF11 and BRD4 with ARRY-520 and JQ1 reduced MPNST cell viability, synergistically killing a much higher proportion of MPNST cells than control fibroblasts. In addition, genetic suppression of KIF15 conferred an increased sensitivity to KIF11 inhibitors alone or in combination with JQ1.

The mitotic spindle kinesins KIF11 and KIF15 and the cytokinetic kinesin KIF23 play a clear role in maintaining MPNST cell survival and may represent potential therapeutic vulnerabilities. Although further in vivo evidences are still mandatory, we propose a simultaneous suppression of KIF11, KIF15, and BRD4 as a potential therapy for MPNSTs.

• BRD4 inhibitor
• KIF11 inhibitor
• KIF15
• combined treatment
• malignant peripheral nerve sheath tumor (MPNST)

• Bioinformatics
• Breast cancer
• PTTG1
• PTTG2
• PTTG3

Low-grade gliomas (LGGs) are a highly heterogeneous group of slow-growing, lethal, diffusive brain tumors. Temozolomide (TMZ) is a frequently used primary chemotherapeutic agent for LGGs. Currently there is no consensus as to the optimal biomarkers to predict the efficacy of TMZ, which calls for decision-making for each patient while considering molecular profiles. Low-grade glioma data sets were retrieved from The Cancer Genome Atlas. Cox regression and survival analyses were applied to identify clinical features significantly associated with survival. Subsequently, Ordinal logistic regression, co-expression, and Cox regression analyses were applied to identify genes that correlate significantly with response rate, disease-free survival, and overall survival of patients receiving TMZ as primary therapy. Finally, gene expression and methylation analyses were exploited to explain the mechanism between these gene expression and TMZ efficacy in LGG patients. Overall survival was significantly correlated with age, Karnofsky Performance Status score, and histological grade, but not with IDH1 mutation status. Using 3 distinct efficacy end points, regression and co-expression analyses further identified a novel 4-gene signature of ASPM, CCNB1, EXO1, and KIF23 which negatively correlated with response to TMZ therapy. In addition, expression of the 4-gene signature was associated with those of genes involved in homologous recombination. Finally, expression and methylation profiling identified a largely unknown olfactory receptor OR51F2 as potential mediator of the roles of the 4-gene signature in reducing TMZ efficacy. Taken together, these findings propose the 4-gene signature as a novel panel of efficacy predictors of TMZ therapy, as well as potential downstream mechanisms, including homologous recombination, OR51F2, and DNA methylation independent of MGMT.

• ASPM
• CCNB1
• EXO1
• KIF23
• OR51F2
• brain tumor
• homologous recombination
• low-grade glioma
• temozolomide

• Adult
• Aged
• Animals
• Carcinogenesis/genetics
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Cell Line, Tumor
• Cell Proliferation/genetics
• Epithelial-Mesenchymal Transition/genetics
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• Microarray Analysis
• Middle Aged
• RNA, Long Noncoding/physiology
• Uterine Cervical Neoplasms/genetics
• Uterine Cervical Neoplasms/pathology

• Gene Expression Omnibus
• bioinformatics analysis
• diagnosis
• microarray
• nasopharyngeal carcinoma

• KIF23
• Methylation
• MiR-424/503 cluster
• ovarian cancer

• 3' Untranslated Regions
• Carcinogenesis/genetics
• Carcinoma, Ovarian Epithelial/genetics
• Carcinoma, Ovarian Epithelial/metabolism
• Carcinoma, Ovarian Epithelial/pathology
• Cell Cycle/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• DNA Methylation
• Databases, Nucleic Acid
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• MicroRNAs/chemistry
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Microtubule-Associated Proteins/genetics
• Microtubule-Associated Proteins/metabolism
• Oligonucleotide Array Sequence Analysis
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/pathology
• Promoter Regions, Genetic
• Protein Interaction Maps

Objective: The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients.

Methods: All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators.

Results: In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [EZH2], kinesin family member 23 [KIF23], chromobox 2 [CBX2], centrosomal protein 55 [CEP55], cell division cycle 25A [CDC25A], and claspin [CLSPN]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P<0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation.

Conclusions: Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.

• TCGA.
• bioinformatics
• competing endogenous RNA
• hepatocellular carcinoma
• prognosis

• KIF
• KIF11
• NCH93
• kinesin
• meningioma

Gastric cancer (GC) is one of the most aggressive malignant tumors with low early diagnosis and high metastasis. Despite progress in treatment, to combat this disease, a better understanding of the underlying mechanisms and novel therapeutic targets is needed. KIF23, which belongs to the KIF family, plays a vital role in various cell processes, such as cytoplasm separation and axon elongation. Nowadays, KIF23 has been found to be highly expressed in multiple tumor tissues and cells, suggesting a potential link between KIF23 and tumorigenesis. Herein, we reported that KIF23 expression was correlated with poor prognosis of gastric cancer and found an association between KIF23 and pTNM stage. An in vitro assay proved that the proliferation of gastric cancer cells was significantly inhibited, which is caused by KIF23 depletion. Additionally, knockdown of KIF23 resulted in a marked inhibition of cell proliferation of gastric cancer in mice, with significant downregulation of Ki67 and PCNA expression. In conclusion, these data indicate that KIF23 is a potential therapeutic target for gastric cancer treatment.

To determine the prognostic significance of kinesin superfamily gene (KIF) expression in patients with brain cancer, including low-grade glioma (LGG) and glioblastoma (GBM), we comprehensively analyzed KIFs in 515 LGG and 595 GBM patients. Among KIFs, KIF4A, 9, 18A, and 23 showed significant clinical implications in both LGG and GBM. The mRNA and protein expression levels of KIF4A, 9, 18A, and 23 were significantly increased in LGG and GBM compared with those in the normal control groups. The mRNA expression levels of KIF4A, 9, 18A, and 23 in LGG were significantly increased in the high-histologic-grade group compared with those with a low histologic grade. Genomic analysis showed that the percent of mRNA upregulation of KIF4A, 9, 18A, and 23 was higher than that of other gene alterations, including gene amplification, deep deletion, and missense mutation. In addition, LGG patients with KIF4A, 18A, and 23 gene alterations were significantly associated with a poor prognosis. In survival analysis, the group with high expression of KIF4A, 9, 18A, and 23 mRNA was significantly associated with a poor prognosis in both LGG and GBM patients. Gene Set Enrichment Analysis (GSEA) revealed that high mRNA expression of KIF4A, 18A, and 23 in LGG and GBM patients showed significant positive correlations with the cell cycle, E2F targets, G₂M checkpoint, Myc target, and mitotic spindle. By contrast, high mRNA expression of KIF9 in both LGG and GBM patients was significantly negatively correlated with the cell cycle, G₂M checkpoint, and mitotic spindle pathway. However, it was significantly positively correlated with EMT and angiogenesis. This study has extended our knowledge of KIF4A, 9, 18A, and 23 in LGG and GBM and shed light on their clinical relevance, which should help to improve the treatment and prognosis of LGG and GBM.

Oral cancer refers to the malignant tumors that occur in the oral cavity, of which 80% are squamous cell carcinomas. The incidence of oral cancer accounts for ~5% of the incidence of systemic malignancies, with rapid progression, extensive infiltration and poor prognosis. In the present study, Kinesin family member (KIF)20B, a member of Kinesin-6 family, was identified as a potential biomarker which could promote cancer progression. A total of 82 patients were recruited and KIF20B expression levels were investigated by immunohistochemistry, and were divided into high and low groups based on the median of KIF20B expression levels. The clinicopathological features and survival-associated data of the two groups were analyzed and the results were provided as a table and by a Kaplan-Meier plot, respectively. Additionally, KIF20B was successfully silenced in two tongue cancer cell lines, CAL-27 and TCA-8113. MTT and colony formation assay were performed to determine the changes of cell proliferation in knocked down-KIF20B cell lines. In addition, proliferation-associated proteins Ki67 and PCNA were investigated, by western blotting. In animal experiments, subcutaneous tumor formation was performed with control cells and cells with knocked down KIF20B, to determine the inhibitory effect of KIF20B in vivo. Firstly, it was found that there was significantly high expression levels of KIF20B in tongue cancer patients (P<0.05). Patients with high expression of KIF20B had poorer clinicopathological results including tumor differentiation level, lymph node metastasis and clinical stages. The overall survival and relapse-free survival of high-expression group were also poor. Secondly, after successful establishment of cells with knocked down KIF20B, this resulted in a notable reduction in cell proliferation in vitro. Subsequent western blotting further confirmed that Ki67 and PCNA expression levels had a significant decline. Finally, it was demonstrated that knocking down KIF20B could inhibit tumor volume growth in vivo. In conclusion, the high level of KIF20B in oral squamous cell carcinoma was significantly associated with poor clinicopathological features and survival. KIF20B might promote cancer development through enhancing cell proliferation in vitro, and might be a potential biomarker of oral squamous cell carcinoma.

• Cancer therapy
• MTA resistance
• Mitotic exit

This study aims to reveal the regulation network of lncRNAs-miRNAs-mRNA in endometrial carcinoma (EC), to investigate the underlying mechanisms of EC occurrence and progression, to screen prognostic biomarkers.

RNA-seq and miRNA-seq data of endometrial carcinoma were downloaded from the TCGA database. Edge.R package was used to screen differentially expressed genes. A database was searched to determine differentially expressed lncRNA-miRNA and miRNA-mRNA pairs, to construct the topological network of ceRNA, and to elucidate the key RNAs that are for a prognosis of survival.

We screened out 2632 mRNAs, 1178 lncRNAs and 189 miRNAs that were differentially expressed. The constructed ceRNA network included 97 lncRNAs, 20 miRNAs and 73 mRNAs. Analyzing network genes for associations with prognosies revealed 169 prognosis-associated RNAs, including 92 lncRNAs, 16miRNAs and 61 mRNAs.

Our results reveal new potential mechanisms underlying the carcinogenesis and progression of endometrial carcinoma.

• Endometrial carcinoma
• Prognostic biomarker
• ceRNA network

The authors apply telomeric chromatin analysis to identify factors that accumulate at telomeres during cellular transformation, promoting telomere replication and repair and counteracting oncogene-borne telomere replication stress.

Telomeres play crucial roles during tumorigenesis, inducing cellular senescence upon telomere shortening and extensive chromosome instability during telomere crisis. However, it has not been investigated if and how cellular transformation and oncogenic stress alter telomeric chromatin composition and function. Here, we transform human fibroblasts by consecutive transduction with vectors expressing hTERT, the SV40 early region, and activated H-RasV12. Pairwise comparisons of the telomeric proteome during different stages of transformation reveal up-regulation of proteins involved in chromatin remodeling, DNA repair, and replication at chromosome ends. Depletion of several of these proteins induces telomere fragility, indicating their roles in replication of telomeric DNA. Depletion of SAMHD1, which has reported roles in DNA resection and homology-directed repair, leads to telomere breakage events in cells deprived of the shelterin component TRF1. Thus, our analysis identifies factors, which accumulate at telomeres during cellular transformation to promote telomere replication and repair, resisting oncogene-borne telomere replication stress.

非小细胞肺癌（non-small cell lung cancer, NSCLC）是全球引起死亡的最重要原因之一。大多数患者发现时处于中晚期，预后较差。本研究拟探讨驱动蛋白超家族23（kinesin family member 23, KIF23）在NSCLC中的表达及意义。

收集Oncomine数据库中关于KIF23的信息，并对目前数据库中资料进行二次分析，对其在NSCLC中的作用进行荟萃分析。利用Kaplan-Meier Plotter进行患者生存周期分析。

Oncomine数据库中共收集了447项不同类型的研究结果，其中关于KIF23表达有统计学差异的研究结果有67个，KIF23表达增高的研究有64项、表达降低的研究有3项。共有16项研究涉及KIF23在NSCLC癌组织和正常组织中的表达，共包括1, 189个样本，与对照组相比，KIF23在NSCLC细胞癌中高表达（P＜0.05）。不仅如此，KIF23表达量与NSCLC总体生存率存在相关性，高表达KIF23的患者总体生存率较差，低表达KIF23的患者预后较好（P＜0.05）。进一步亚组分析发现，KIF23表达水平对肺腺癌患者预后有显著影响，而在鳞癌患者中，其表达水平对预后无显著影响。

我们通过对Oncomine基因芯片数据库中肿瘤相关基因信息的深入挖掘，提出KIF23在NSLCL组织中高表达，且与NSCLC预后有关，可能为肿瘤药物的开发提供重要理论依据。

• Kinesin family member 23
• Lung neoplasms
• Oncomine

• Mesothelioma
• diagnostic marker
• drug inhibitor
• overexpression
• prognostic marker
• therapeutic target

Kinesin family member 23 (KIF23), a nuclear protein and a key regulator of cellular cytokinesis, has been found to be overexpressed as an oncogene in glioma. However, the prognostic and clinicopathological features of glioma with KIF23 expression was not clear yet. Here, we analyzed KIF23 expression pattern by using whole genome mRNA expression microarray data from Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn), and found that KIF23 overexpression was significantly associated with high grade glioma as well as the higher mortality in survival analysis (log-rank test, p<0.01). The results of the three other validation datasets showed similar findings. Furthermore, KIF23 also served as an independent prognostic biomarker in glioma patients. Finally, functional assay showed that reduction of KIF23 suppressed glioma cell proliferation both in vivo and vitro. Additionally, we found that KIF23 was regulated by TCF-4 at transcriptionally level. Therefore, this evidence indicates KIF23 over-expression is associated with glioma malignancy and conferred a worse survival time in glioma, which suggests KIF23 is a new novel prognostic biomarker with potential therapeutic implications in glioma.

• KIF23
• TCF-4
• glioma
• prognostic
• proliferation

KIF23 was recently suggested to be a potential molecular target for the treatment of lung cancer. This proposal is based on elevated expression of KIF23 in several tumors affecting breast, lung, brain, and liver, and also on the presence of KIF23 mutations in melanoma and colorectal cancer. Recently, we identified a mutation in the KIF23 gene causing a rare hereditary form of dyserythropoietic anemia (CDA III) with predisposition to blood cancer. We suggested that KIF23 overexpression in tumors might be due to the presence of activating somatic mutations, and therefore, mutation screening of the KIF23 in 15 non-small-cell lung cancer (NSCLC) cases with elevated expression level of KIF23 was undertaken. Eight sequence variants were found in all samples. Furthermore, one variant was present in two cases, and one variant was case specific. Nine variants were previously reported while one variant lacks frequency information. Nine of ten cases available for single nucleotide polymorphism-array analysis demonstrated aberrant karyotypes with additional copy of entire chromosome 15. Thus, no activating somatic mutations in coding regions of the KIF23 were found. Furthermore, no mutations were detected in cell cycle genes homology region in KIF23 promoter responsible for p53-dependent repression of KIF23 expression. We showed that the elevated level of KIF23 could be due to additional copy of chromosome 15 demonstrated in 90% of NSCLC cases analyzed in this study. Considering the crucial role of KIF23 in the final step of mitosis, the gene is a potential molecular marker, and for better understanding of its role in cancer development, more tumors should be analyzed.

• CNA
• KIF23
• copy number alteration
• lung cancer
• mutation
• overexpression

The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1. We demonstrate that six mitotic kinesins and two microtubule-associated non-motor proteins (MAPs) CEP55 and PRC1 are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cells. Suppression of KIF23 and PRC1 strongly suppressed proliferation of MDA-MB-231 cells. The set of MMB-FOXM1 regulated kinesins genes and 4 additional kinesins which we referred to as the mitotic kinesin signature (MKS) is linked to poor outcome in breast cancer patients. Thus, mitotic kinesins could be used as prognostic biomarker and could be potential therapeutic targets for the treatment of breast cancer.

• B-MYB
• DREAM
• FOXM1
• MuvB
• kinesin

• DEPDC1
• Malignant glioma
• Molecular target therapy
• Oncoantigen
• Vaccine therapy

• Access to Information
• Antineoplastic Agents/therapeutic use
• Cell Line, Tumor
• Cholesterol/biosynthesis
• Databases, Protein
• Docetaxel
• Female
• Humans
• Internet
• Liver/drug effects
• Male
• Mutation
• Prostatic Neoplasms/drug therapy
• Proteome
• RNA Splicing
• Taxoids/therapeutic use