Translating bioinformatics in oncology: guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis

Itzel, Timo; Scholz, Peter; Maass, T; Krupp, Markus; Marquardt, Jens U.; Strand, Susanne; Becker, Diana; Staib, Frank; Binder, Harald; Roessler, Stephanie; Wang, Xin Wei; Thorgeirsson, Snorri S.; Müller, Martina; Galle, Peter R.; Teufel, Andreas

doi:10.1093/bioinformatics/btu586

Cited by 56 publications

(54 citation statements)

References 39 publications

(39 reference statements)

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“…KIF18B, a member of the Kinesin‐8 family in humans, has been shown to express in a cell cycle‐dependent manner and supposed to take a critical role in cell division . The overexpression of KIF18B in hepatic carcinoma and cervical cancer has been reported recently, hinting that it is closely correlated with tumor progression. Our study first reported that KIF18B is highly expressed in cutaneous melanoma and is correlated with shorter overall survival time.…”

Section: Discussionsupporting

confidence: 93%

“…Stout et al identified that KIF18B is a critical regulator of astral microtubule dynamics. Previously, bioinformatic analyses by Itzel et al found that KIF18B is increased in breast, lung, liver, ovarian and renal cancer. In vitro and in vivo biological experiments showed that KIF18B functioned as a promoter in cervical cancer proliferation and metastasis .…”

Section: Introductionmentioning

confidence: 99%

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

Yan

Zhu

Zhang

2019

J Biochem & Molecular Tox

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Yan

Zhu

Zhang

2019

J Biochem & Molecular Tox

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“…Previous study showed that a member of the cell division cycleassociated proteins, CDCA3, was associated with the expression of KIF18B (Itzel et al, 2015). We focused on another cell cycle regulator, CDCA8, after the screening of CHIP-CHIP assays (data not shown).…”

Section: Kif18b Promotes Pdac Through Transcriptionally Activatingmentioning

confidence: 99%

“…KIF18B was initially identified as a member of the kinesin family (Itzel et al, 2015). As a plus end-directed motor protein, KIF18B moves along microtubules and controls MT end accumulation through EB1 (McHugh et al, 2018;Stout et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Zhang

et al. 2019

Journal Cellular Physiology

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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. K E Y W O R D SCDCA8, KIF18B, pancreatic ductal adenocarcinoma, proliferation, therapeutic target

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“…Several computational methods have been developed to infer relationships between genes based on gene expression data. These range from methods for inferring co-expression relationships between pairs of genes 1 to methods for inferring a biological or disease process for a gene based on other genes (either using clustering or guilt by association 2 ) to causality inferences 3, 4 and pathway reconstruction method 5 . To date, each of these tasks was handled by a different computational framework.…”

Section: Introductionmentioning

confidence: 99%

Deep learning for inferring gene relationships from single-cell expression data

Yuan

Bar‐Joseph

2018

Preprint

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Several methods were developed to mine gene-gene relationships from expression data. Examples include correlation and mutual information methods for co-expression analysis, clustering and undirected graphical models for functional assignments and directed graphical models for pathway reconstruction. Using a novel encoding for gene expression data, followed by deep neural networks analysis, we present a framework that can successfully address all these diverse tasks. We show that our method, CNNC, improves upon prior methods in tasks ranging from predicting transcription factor targets to identifying disease related genes to causality inference.CNNC's encoding provides insights about some of the decisions it makes and their biological basis. CNNC is flexible and can easily be extended to integrate additional types of genomics data leading to further improvements in its performance.Supporting website with software and data: https://github.com/xiaoyeye/CNNC.

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Translating bioinformatics in oncology: guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 56 publications

References 39 publications

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

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

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

Deep learning for inferring gene relationships from single-cell expression data

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