KIF18b-dependent hypomethylation of PARPBP gene promoter enhances oxaliplatin resistance in colorectal cancer.

As the new platinum drug oxaliplatin has been widely used in clinical treatment of colorectal cancer (CRC), oxaliplatin resistance has become a burning problem. In this study, higher expression of PARP-1 binding protein (PARPBP) was detected in oxaliplatin-resistant CRC (OR-CRC) cells than in non-resistant cells. Further research showed that kinesin family member 18 b (KIF18b) induced the overexpression of PARPBP, sustaining oxaliplatin resistance in OR-CRC cells. Through exploring the PARPBP gene promoter, we found that SP1-recruited DNMT3b methylated PARPBP promoter to suppress transcription in CRC cells, and increased KIF18b attenuated the recruitment of DNMT3b to PARPBP promoter by directly interacting with SP1 in OR-CRC cells. Clinical analysis suggested a positive relationship between KIF18b and PARPBP in CRC tissues and indicated poor prognosis in CRC patients with high level of KIF18b or PARPBP. In summary, KIF18b-induced PARPBP contributes to the resistant phenotype of OR-CRC.

KIF18B promotes hepatocellular carcinoma progression through activating Wnt/ß-catenin-signaling pathway.

This study aimed to investigate the functional roles of kinesin family member 18B (KIF18B) in hepatocellular carcinoma (HCC) development, as well as the related molecular mechanisms. Tissue specimens were collected from 105 patients with HCC, and the messenger RNA (mRNA) and protein levels of KIF18B were detected using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The χ2 test was performed to estimate the association of KIF18B with clinical characteristics of patients with HCC. Effects of KIF18B expression on biological behaviors of HCC cells were detected by clone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and transwell assays. The expression patterns of proteins were investigated using Western blot analysis. HCC tissues and cell lines showed significant upregulation of KIF18B at both mRNA and protein levels (p > .05, for all). Furthermore, the elevated KIF18B expression was positively correlated with the tumor-node-metastasis stage (p = .015) and lymph node metastasis (p = .007). Knockdown of KIF18B might suppress HCC cell clone formation, proliferation, migration, and invasion in vitro. Besides, the activity of Wnt/ß-catenin pathway was also significantly inhibited after the KIF18B knockdown. However, the antitumor actions caused by KIF18B knockdown might be reversed by lithium chloride treatment, which was the inducer of Wnt/ß-catenin-signaling pathway. KIF18B may serve as an oncogene in HCC through enhancing the activity of Wnt/ß-catenin pathway.

KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8.

Pancreatic cancer is one of the malignant tumors with the worst prognosis, and the 5-year survival rate of this disease is less than 1%. About 90% of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), and targeting therapy has become a promising treatment for PDAC in recent years. To improve the survival rate, novel therapeutic targets for PDAC are still urgently needed. KIF18B was initially identified as a member of the kinesin family and involved in multiple cellular processes, such as separation of chromosomes in mitosis. Recently, it was found that KIF18B was involved in the growth and development of multiple cancers. However, the potential link between KIF18B and PDAC is still unclear. In this study, we demonstrated that KIF18B was highly expressed in human PDAC tissues, and related with the poor prognosis and clinical features, such as tumor size (*p = .013) and pTNM stage (*p = .025), of patients with PDAC. We further found that KIF18B knockdown blocked the cell proliferation of PDAC in vitro and in vivo, and the cell cycle was arrested caused by KIF18B depletion. Additionally, we also found that KIF18B bound to the promoter region of the cell division cycle associated 8 and thus activated its transcription. Taken together, this study explored the molecular mechanism underlying KIF18B promoting PDAC and provided a novel therapeutic target of this disease.

Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma.

Melanoma is the most aggressive type of cutaneous tumor and the occurrence of metastasis makes it resistant to almost all available treatment and becomes incorrigible. Hence, identifying metastasis-related biomarkers and effective therapeutic targets will assist in preventing metastasis and ameliorating cutaneous melanoma. In our present study, we reported kinesin family member 18B (KIF18B) as a novel contributor in cutaneous melanoma proliferation and metastasis, and it was found to be of great significance in predicting the prognosis of cutaneous melanoma patients. Bioinformatics analysis based on ONCOMINE, The Cancer Genome Atlas, and Genotype-Tissue Expression database revealed that KIF18B was highly expressed in cutaneous melanoma and remarkably correlated with unfavorable clinical outcomes. Consistently, the results of the quantitative real-time polymerase chain reaction exhibited that the expression of KIF18B was significantly higher in cutaneous melanoma cell lines than that in normal cells. In vitro, biological assays found that knockdown of KIF18B in cutaneous melanoma cells noticeably repressed cell proliferation, migration, and invasion, while inducing cell apoptosis. Moreover, the protein expression of E-cadherin was enhanced while the expression of N-cadherin, vimentin, and Snail was decreased in M14 cells after knocking down KIF18B. In addition, the phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular-signal-regulated kinase (ERK) was significantly suppressed in M14 cells with silenced KIF18B. Above all, our results indicated that the repression of cutaneous melanoma cell migration and proliferation caused by KIF18B depletion suggested an oncogenic role of KIF18B in cutaneous melanoma, which acts through modulating epithelial-mesenchymal transition and ERK/PI3K pathway.

Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation.

Inhibition of the microtubule (MT) motor protein Eg5 results in a mitotic arrest due to the formation of monopolar spindles, making Eg5 an attractive target for anti-cancer therapies. However, Eg5-independent pathways for bipolar spindle formation exist, which might promote resistance to treatment with Eg5 inhibitors. To identify essential components for Eg5-independent bipolar spindle formation, we performed a genome-wide siRNA screen in Eg5-independent cells (EICs). We find that the kinase Aurora A and two kinesins, MCAK and Kif18b, are essential for bipolar spindle assembly in EICs and in cells with reduced Eg5 activity. Aurora A promotes bipolar spindle assembly by phosphorylating Kif15, hereby promoting Kif15 localization to the spindle. In turn, MCAK and Kif18b promote bipolar spindle assembly by destabilizing the astral MTs. One attractive way to interpret our data is that, in the absence of MCAK and Kif18b, excessive astral MTs generate inward pushing forces on centrosomes at the cortex that inhibit centrosome separation. Together, these data suggest a novel function for astral MTs in force generation on spindle poles and how proteins involved in regulating microtubule length can contribute to bipolar spindle assembly.

Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8.

Kinesin-8s are plus-end-directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are "ultraprocessive," a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end-directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of motility. Diffusion is promoted by the tail domain, which also contains a second MT-binding site that decreases the off rate of the motor from the MT lattice. In cells, Kif18B concentrates at the extreme tip of a subset of MTs, superseding EB1. Our data demonstrate that kinesin-8 motors use diverse design principles to target MT plus ends, which likely target them to the plus ends of distinct MT subpopulations in the mitotic spindle.

KIF18B: an important role in signaling pathways and a potential resistant target in tumor development.

KIF18B is a key member of the kinesin-8 family, involved in regulating various physiological processes such as microtubule length, spindle assembly, and chromosome alignment. This article briefly introduces the structure and physiological functions of KIF18B, examines its role in malignant tumors, and the associated carcinogenic signaling pathways such as PI3K/AKT, Wnt/ß-catenin, and mTOR pathways. Research indicates that the upregulation of KIF18B enhances tumor malignancy and resistance to radiotherapy and chemotherapy. KIF18B could become a new target for anticancer drugs, offering significant potential for the treatment of malignant tumors and reducing chemotherapy resistance.

The cytotoxic potential of sinapic acid on luminal A breast cancer; a computational and experimental pharmacology approach.

Breast cancer is a highly concerning and prevalent disease that impacts a significant proportion of women worldwide, whose repeated exposure to therapies leads to resistance for drugs; making it alarming to identify novel chemotherapeutic agents. Sinapic acid is a phenolic acid that occurs naturally and is known to exhibit cytotoxic action in a variety of cancer cell types. In the present study, we utilized cell cytotoxicity assays to assess the cytotoxic potential of sinapic acid on various breast cancer subtypes. In addition, we assessed the cell migration rate, cell apoptosis, and cell cycle phases. Moreover, we utilized multiple system biology tools to predict the potential targets, and molecular docking was performed on the hub targets followed by molecular dynamic (MD) simulations. Cytotoxicity assay was performed on cell lines MCF7, T47D, MDA-MB-468, and SKBR3 at different time exposures of 24, 48, and 96 h. Our results revealed sinapic acid to be potent on MCF7 and T47D cell lines. The cell cycle analysis and cell apoptotic assays revealed sinapic acid to cause cell death by apoptosis majorly in the G0/G1 phase. Computational biology revealed KIF18B and VKORC1 to possess the highest binding affinity of -6.5 and -7.5 kcal/mol; displayed stable trajectories on MD run. The cytotoxicity of sinapic acid on luminal A cell lines may be due to the modulation of VKORC1 and KIF18B with major cell death in the G0/G1 phase. However, the mechanism has been proposed via in silico tools, which need further validation using wet lab protocols.Communicated by Ramaswamy H. Sarma.

Multi-omics analysis reveals the association between elevated KIF18B expression and unfavorable prognosis, immune evasion, and regulatory T cell activation in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. The expression profile and functions of kinesin family member 18B (KIF18B) remain unclear in NPC. Methods: Bulk and single-cell transcriptome data for NPC were downloaded. KIF18B expression differences in NPC and normal tissues and its prognostic value were validated by immunohistochemistry and Cox model. We performed multi-faceted functional enrichment analysis on KIF18B. Immune infiltration was analyzed comprehensively by the CIBERSORT, EPIC, and quanTIseq algorithms and the BisqueRNA package and confirmed by immunofluorescence assay. The intercellular communication were investigated by the CellChat package. We explored the dynamics of KIF18B expression by pseudotime trajectory. M6A modification analysis rely on SRAMP platform. The treatment response were evaluated by Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore and IC50 value. Results: KIF18B overexpression in NPC led to unfavorable prognosis, and significantly associated with advanced T, N, and stage classifications. Functional analysis demonstrated that KIF18B was involved in immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification and therapeutic responses. The deconvolution algorithm indicated that activated regulatory T cells (Tregs) had the strongest positive correlation with KIF18B among immune cells (R = 0.631). Validated by immunofluorescence assay, the high KIF18B expression group displayed a notable rise in Tregs infiltration, accompanied by a substantial decrease in the infiltration of CD8+ T cells and macrophages. In the intercellular communication network, malignant cells with high KIF18B expression implicated in more interactions, and activated and recruited Tregs by modulating cytokines, chemokines, and immune checkpoints. KIF18B was upregulated in more advanced malignant cells and influenced EMT by regulating ITGA6, VIM, and ZEB1/2. KIF18B expression was positively related to m6A "writer" and "reader" genes, and negatively related to "eraser" genes. The KIF18B high expression group exhibited a higher TIDE score and elevated IC50 values for the commonly used chemotherapy drugs, gemcitabine, oxaliplatin, and 5-fluorouracil. Conclusion: KIF18B is a significant prognostic marker in NPC, and may modulate immune evasion and EMT. M6A modification may account for the aberrant overexpression of KIF18B in NPC. Furthermore, KIF18B may predict response to immunotherapy and chemotherapy.

miR-139-3p/Kinesin family member 18B axis suppresses malignant progression of gastric cancer.

miR-139-3p exerts tumor-suppressing functions in various cancers. We analyzed and identified that miR-139-3p expression was notably low in gastric cancer (GC) via edgeR differential analysis based on The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction (qRT-PCR) assay. The binding relationship between Kinesin Family Member 18B (KIF18B) and miR-139-3p was predicted by bioinformatics databases, and verified through dual-luciferase assay. Western blot and qRT-PCR results also indicated that miR-139-3p restrained KIF18 expression at mRNA and protein levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, transwell, flow cytometry assays were introduced to evaluate cell proliferation, migration, invasion, and cell cycle, respectively, where the results indicated that upregulating miR-139-3p inhibited proliferative, migratory, and invasive abilities of GC cells, while caused cell-cycle arrest. Moreover, the results of rescue experiments illustrated that miR-139-3p hampered the progression of GC cells by targeting and suppressing KIF18B. To sum up, we concluded that miR-139-3p suppressed GC progression by targeting KIF18B.

Optogenetic EB1 inactivation shortens metaphase spindles by disrupting cortical force-producing interactions with astral microtubules.

Chromosome segregation is accomplished by the mitotic spindle, a bipolar micromachine built primarily from microtubules. Different microtubule populations contribute to spindle function: kinetochore microtubules attach and transmit forces to chromosomes, antiparallel interpolar microtubules support spindle structure, and astral microtubules connect spindle poles to the cell cortex.1,2 In mammalian cells, end-binding (EB) proteins associate with all growing microtubule plus ends throughout the cell cycle and serve as adaptors for diverse +TIPs that control microtubule dynamics and interactions with other intracellular structures.3 Because binding of many +TIPs to EB1 and thus microtubule-end association is switched off by mitotic phosphorylation,4-6 the mitotic function of EBs remains poorly understood. To analyze how EB1 and associated +TIPs on different spindle microtubule populations contribute to mitotic spindle dynamics, we use a light-sensitive EB1 variant, π-EB1, that allows local, acute, and reversible inactivation of +TIP association with growing microtubule ends in live cells.7 We find that acute π-EB1 photoinactivation results in rapid and reversible metaphase spindle shortening and transient relaxation of tension across the central spindle. However, in contrast to interphase, π-EB1 photoinactivation does not inhibit microtubule growth in metaphase but instead increases astral microtubule length and number. Yet in the absence of EB1 activity, astral microtubules fail to engage the cortical dynein/dynactin machinery, and spindle poles move away from regions of π-EB1 photoinactivation. In conclusion, our optogenetic approach reveals mitotic EB1 functions that remain hidden in genetic experiments, likely due to compensatory molecular systems regulating vertebrate spindle dynamics.

KIF18B is a Prognostic Biomarker and Correlates with Immune Infiltrates in Pan-Cancer.

Background: Cancer is one of the deadliest diseases at present. Although effective screening and treatment can save lives to a certain extent, our knowledge of the disease is far from sufficient. KIF18B is a member of the kinesin-8 superfamily and plays a conserved regulatory role in the cell cycle. KIF18B reportedly functions as an oncogene in some human cancers, but the correlations between KIF18B and prognosis and immune-infiltrates in different cancers remain unclear. Methods: Data were collected from the TCGA, GTEx, CCLE, TIMER, and GSEA databases. The expression difference, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs), tumor microenvironment (TME), immune cell infiltration, and gene co-expression of KIF18B were analyzed using the R language software. Results: KIF18B was widely upregulated in cancers, compared with normal tissues, and high KIF18B expression was associated with unfavorable prognoses. TMB, MSI, MMRs, and DNA methylation correlated with KIF18B dysregulation in cancers. KIF18B correlated closely with tumor immunity and interacted with different immune cells and genes in different cancer types. Conclusion: KIF18B could be used as a prognostic biomarker for determining prognosis and immune infiltration in pan-cancer.

Silencing of KIF18B restricts proliferation and invasion and enhances the chemosensitivity of breast cancer via modulating Akt/GSK-3ß/ß-catenin pathway.

Kinesin family member 18B (KIF18B) is a new tumor-associated protein that contributes to the carcinogenesis of multiple malignancies. However, the detailed relevance of KIF18B in breast cancer has not been fully elucidated. This work aimed was to evaluate a possible relationship between KIF18B and breast cancer progression. Our findings show KIF18B is increased in breast cancer and demonstrate that high KIF18B level predicts a reduced survival rate. Cellular functional studies revealed that knockdown of KIF18B markedly reduces the proliferation, invasion, and epithelial-mesenchymal transition of breast cancer cells and enhances their chemosensitivity toward doxorubicin. Further studies showed that KIF18B modulates the level of phospho-Akt, phospho-glycogen synthase kinase-3ß, and ß-catenin. Notably, suppression of Akt abolished KIF18B-overexpression-induced increases in activation of Wnt/ß-catenin pathway. In addition, re-expression of ß-catenin reversed KIF18B-silencing-induced cancer-promoting effect. In vivo animal experiments elucidated that knockdown of KIF18B significantly weakened the tumorigenicity of breast cancer cells. Taken together, data of this study illustrate that KIF18B exerts a potential cancer-promoting function in breast cancer via enhancement of Wnt/ß-catenin pathway through modulation of the Akt/GSK-3ß axis.

KIF18B as a regulator in tumor microenvironment accelerates tumor progression and triggers poor outcome in hepatocellular carcinoma.

BACKGROUND: The tumor microenvironment plays an important role in the progression and recurrence of tumors and immunotherapy outcomes. The use of immune checkpoint blockers to improve the overall survival rate of patients with advanced hepatocellular carcinoma has yielded inconsistent outcomes. We examined the tumor microenvironment-related genes for their clinical significance and biological functions in hepatocellular carcinoma. METHODS: Bioinformatic analysis was performed to screen the differentially expressed genes and to identify the core gene of the tumor microenvironment in hepatocellular carcinoma. The expression of KIF18B in hepatocellular carcinoma cell lines and tumor samples was determined using western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The malignancy-promoting ability of KIF18B was evaluated using Cell Counting Kit-8, colony formation, cell proliferation, migration and invasion, and xenograft tumor assays. RESULTS: KIF18B was identified as one of the core genes in the hepatocellular carcinoma microenvironment and was significantly associated with infiltrating immune cell subtypes and tumor cell stemness. Upregulation of KIF18B was associated with poor clinicopathological characteristics and poor patient outcomes; its downregulation inhibited the proliferation ability of hepatocellular carcinoma cells, which was consistent with the findings of in vivo experiments. Knockdown of KIF18B inhibited epithelial-mesenchymal transition which reduced the migration and invasion abilities of tumor cells. A pulmonary metastasis model confirmed that the downregulation of KIF18B inhibited hepatocellular carcinoma cell metastasis in vivo. CONCLUSION: KIF18B could be a useful marker for determining the treatment outcomes of immune checkpoint blockers in the context of hepatocellular carcinoma.

The nuclear kinesin KIF18B promotes 53BP1-mediated DNA double-strand break repair.

53BP1 is recruited to chromatin in the vicinity of DNA double-strand breaks (DSBs). We identify the nuclear kinesin, KIF18B, as a 53BP1-interacting protein and define its role in 53BP1-mediated DSB repair. KIF18B is a molecular motor protein involved in destabilizing astral microtubules during mitosis. It is primarily nuclear throughout the interphase and is constitutively chromatin bound. Our observations indicate a nuclear function during the interphase for a kinesin previously implicated in mitosis. We identify a central motif in KIF18B, which we term the Tudor-interacting motif (TIM), because of its interaction with the Tudor domain of 53BP1. TIM enhances the interaction between the 53BP1 Tudor domain and dimethylated lysine 20 of histone H4. TIM and the motor function of KIF18B are both required for efficient 53BP1 focal recruitment in response to damage and for fusion of dysfunctional telomeres. Our data suggest a role for KIF18B in efficient 53BP1-mediated end-joining of DSBs.

Destabilization of Long Astral Microtubules via Cdk1-Dependent Removal of GTSE1 from Their Plus Ends Facilitates Prometaphase Spindle Orientation.

The precise regulation of microtubule dynamics over time and space in dividing cells is critical for several mitotic mechanisms that ultimately enable cell proliferation, tissue organization, and development. Astral microtubules, which extend from the centrosome toward the cell cortex, must be present for the mitotic spindle to properly orient, as well as for the faithful execution of anaphase and cytokinesis. However, little is understood about how the dynamic properties of astral microtubules are regulated spatiotemporally, or the contribution of astral microtubule dynamics to spindle positioning. The mitotic regulator Cdk1-CyclinB promotes destabilization of centrosomal microtubules and increased microtubule dynamics as cells enter mitosis, but how Cdk1 activity modulates astral microtubule stability, and whether it impacts spindle positioning, is unknown. Here, we uncover a mechanism revealing that Cdk1 destabilizes astral microtubules in prometaphase and thereby influences spindle reorientation. Phosphorylation of the EB1-dependent microtubule plus-end tracking protein GTSE1 by Cdk1 in early mitosis abolishes its interaction with EB1 and recruitment to microtubule plus ends. Loss of Cdk1 activity, or mutation of phosphorylation sites in GTSE1, induces recruitment of GTSE1 to growing microtubule plus ends in mitosis. This decreases the catastrophe frequency of astral microtubules and causes an increase in the number of long astral microtubules reaching the cell cortex, which restrains the ability of cells to reorient spindles along the long cellular axis in early mitosis. Astral microtubules thus must not only be present but also dynamic to allow the spindle to reorient, a state assisted by selective destabilization of long astral microtubules via Cdk1.

Silencing KIF18B enhances radiosensitivity: identification of a promising therapeutic target in sarcoma.

BACKGROUND: Sarcomas are rare heterogeneous tumours, derived from primitive mesenchymal stem cells, with more than 100 distinct subtypes. Radioresistance remains a major clinical challenge for sarcomas, demanding urgent for effective biomarkers of radiosensitivity. METHODS: The radiosensitive gene Kinesin family member 18B (KIF18B) was mined through bioinformatics with integrating of 15 Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. We used radiotherapy-sh-KIF18B combination to observe the anti-tumour effect in sarcoma cells and subcutaneous or orthotopic xenograft models. The KIF18B-sensitive drug T0901317 (T09) was further mined to act as radiosensitizer using the Genomics of Drug Sensitivity in Cancer (GDSC) database. FINDINGS: KIF18B mRNA was significantly up-regulated in most of the subtypes of bone and soft tissue sarcoma. Multivariate Cox regression analysis showed that KIF18B high expression was an independent risk factor for prognosis in sarcoma patients with radiotherapy. Silencing KIF18B or using T09 significantly improved the radiosensitivity of sarcoma cells, delayed tumour growth in subcutaneous and orthotopic xenograft model, and elongated mice survival time. Furthermore, we predicted that T09 might bind to the structural region of KIF18B to exert radiosensitization. INTERPRETATION: These results indicated that sarcomas with low expression of KIF18B may benefit from radiotherapy. Moreover, the radiosensitivity of sarcomas with overexpressed KIF18B could be effectively improved by silencing KIF18B or using T09, which may provide promising strategies for radiotherapy treatment of sarcoma. FUNDINGS: A full list of funding can be found in the Funding Sources section.

KIF18B promotes tumor progression in osteosarcoma by activating ß-catenin.

Objective: Osteosarcoma is a common primary highly malignant bone tumor. Kinesin family member 18B (KIF18B) has been identified as a potential oncogene involved in the development and metastasis of several cancer types. While KIF18B overexpression in osteosarcoma tissue is clearly detected, its specific function in the disease process remains to be established. Methods:KIF18B expression was assessed in osteosarcoma tissues and cells. We additionally evaluated the effects of KIF18B on proliferation, migration, and invasion of osteosarcoma cells, both in vitro and in vivo. Results: Our results showed overexpression of KIF18B in osteosarcoma tissues and cells. Knockdown of KIF18B induced G1/S phase arrest and significantly inhibited proliferation, migration, and invasion of osteosarcoma cells, both in vitro and in vivo. KIF18B regulated ß-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli (APC) tumor suppressor gene in osteosarcoma cells. Conclusions: KIF18B plays a carcinogenic role in osteosarcoma by regulating expression of ß-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC. Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.

Bioinformatics Analysis Suggests the Combined Expression of AURKB and KIF18B Being an Important Event in the Development of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma with high metastatic rate and high mortality rate, needing to find potential therapeutic targets and develop new therapy methods. The bioinformatics analysis was used in this study to find the targets. Firstly, the expression profile of ccRCC obtained from The Cancer Genome Atlas (TCGA) database and GSE53757 dataset were used to identify the significant up-regulated genes. IL20RB, AURKB and KIF18B with the top efficiency of capable of diagnosis ccRCC from para cancer tissue, were over-expressed in ccRCC samples, and expressed increasedly with the development of ccRCC. There was the closest correlation between AURKB and KIF18B in these three over-expressed genes. AURKB (high) or KIF18B (high) were all significantly correlated with higher T, N, M stage, G grade and shorter overall survival (OS) of ccRCC patients. Furthermore, the ccRCC patients with AURKB (high) + KIF18B (high) showed worse clinical characteristics and prognosis. Multivariate COX regression analysis indicated AURKB (high) and KIF18B (high) were all the independent prognostic risk factor without considering the interaction of AURKB and KIF18B. Moreover, considering the combination of each other, only AURKB (high) + KIF18B (high) expression was an independent prognostic risk factor for ccRCC patients, but not other situations. Collectively, AURKB was closely associated with KIF18B, and the combined expression of AURKB and KIF18B may be of great significance in ccRCC.

Kinesin Superfamily Member 18B (KIF18B) Promotes Cell Proliferation in Colon Adenocarcinoma.

BACKGROUND: The role of kinesin superfamily proteins (KIFs) has been reported in a variety of tumors and KIFs contributed to the proliferation of cancer cells. But few studies were focus on colon adenocarcinoma. METHODS: Through bioinformatics analysis and immunohistochemistry (IHC) assays, the expression of KIF18B in colon adenocarcinoma tissues was determined. Stable KIF18B-depleted cell lines were constructed using lentivirus-mediated shRNA of KIF18B. Cell colony formation assay and CCK8 assay were performed to assess cell proliferation degree, and the expression level of KI67 and PCNA was used to indicate cell proliferation in vitro and verified using xenograft tumors in vivo. RESULTS: KIF18B is highly expressed in colon adenocarcinoma tissues and has a negative correlation with the prognosis and tumor grade of colon adenocarcinoma. Interfering with KIF18B inhibits cell proliferation in vitro and in vivo. CONCLUSION: KIF18B can be used as a prognostic marker for colon adenocarcinoma and may be a therapeutic target for colon adenocarcinoma treatment.