KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

Sun, Yue-feng; Wu, Hongli; Shi, Ruifang; Chen, Lin; Meng, Chao

doi:10.1155/2020/6403012

Cited by 10 publications

(7 citation statements)

References 35 publications

(43 reference statements)

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“…Knockdown using siRNA and overexpression of KIF4A resulted in attenuation and promotion of proliferation of HCC cell lines, respectively [ 36 ]. Knockdown of KIF15 by shRNA suppressed proliferation of HCC cell lines in vitro and in mice [ 37 ]. Recent studies reported that an increased expression of KIF4A and KIF15 are potential prognostic factors in prostate cancer [ 38 ] and lung adenocarcinoma [ 39 ], respectively.…”

Section: Discussionmentioning

confidence: 99%

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

Matsushita

Suzuki

Okamura

et al. 2020

Environ Health Prev Med

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Background Various treatments for hepatocellular carcinoma (HCC) are utilized in clinical practice; however, the prognosis is still poor on account of high recurrence rates. DNA methylation levels of CpG islands around promoters (promoter CpGis) inversely regulate gene expression and closely involved in carcinogenesis. As a new strategy, several chemicals globally inhibiting DNA methylation have been developed aiming at reducing DNA methylation levels and maintaining the expression of tumor suppressor genes. On the other hand, since these drugs nonspecifically modify DNA methylation, they can cause serious adverse effects. In order to ameliorate the methods by targeting specific CpGs, information of cancer-related genes that are regulated by DNA methylation is required. Methods We searched candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and which are involved in HCC cases. To do so, we first identified genes whose expression were changed in HCC by comparing gene expressions of 371 HCC tissues and 41 non-tumor tissues using the Cancer Genome Atlas (TCGA) database. The genes were further selected for poor prognosis by log-rank test of Kaplan-Meier plot and for cancer relevance by Pubmed search. Expression profiles of upregulated genes in HCC tissues were assessed by Gene Ontology (GO) analysis. Finally, using DNA methylation data of TCGA database, we selected genes whose promoter DNA methylation levels were inversely correlated with gene expression. Results We found 115 genes which were significantly up- or downregulated in HCC tissues and were associated with poor prognosis and cancer relevance. The upregulated genes were significantly enriched in cell division, cell cycle, and cell proliferation. Among the upregulated genes in HCC, we identified hypomethylation of CpGis around promoters of FANCB , KIF15 , KIF4A , ERCC6L , and UBE2C . In addition, TCGA data showed that the tumor suppressor gene P16 is unexpectedly overexpressed in many types of cancers. Conclusions We identified five candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and associate with cancer cases and poor prognosis in HCC. Modification of site-specific DNA methylation of these genes enables a different approach for HCC treatment with higher selectivity and lower adverse effects.

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Section: Discussionmentioning

confidence: 99%

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

Matsushita

Suzuki

Okamura

et al. 2020

Environ Health Prev Med

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“…During cell division, dysregulation of KIF15 can result in aberrant cell proliferation, tumorigenesis, and tumor aggressiveness (11). Recently, KIF15 has been proven to be over-expressed in various cancers including gastric cancer, hepatocellular carcinoma, and lung adenocarcinoma (12)(13)(14). However, the functions of KIF15 in pan-cancer are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Integrative Pan-Cancer Analysis of KIF15 Reveals Its Diagnosis and Prognosis Value in Nasopharyngeal Carcinoma

Chen

et al. 2022

Front. Oncol.

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BackgroundKIF15 plays a vital role in many biological processes and has been reported to influence the occurrence and development of certain human cancers. However, there are few systematic evaluations on the role of KIF15 in human cancers, and the role of KIF15 in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC) also remains unexplored. Therefore, this study aimed to conduct a pan-cancer analysis of KIF15 and evaluate its diagnostic and prognostic potential in NPC.MethodsThe expression pattern, prognostic value, molecular function, tumor mutation burden, microsatellite instability, and immune cell infiltration of KIF15 were examined based on public databases. Next, the diagnostic value of KIF15 in NPC was analyzed using the Gene Expression Omnibus (GEO) database and immunohistochemistry (IHC). Kaplan–Meier curves, Cox regression analyses, and nomograms were used to evaluate the effects of KIF15 expression on NPC prognosis. Finally, the effect of KIF15 on NPC was explored by in vitro experiments.ResultsThe expression of KIF15 was significantly upregulated in 20 out of 33 cancer types compared to adjacent normal tissue. Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analysis showed that KIF15 could participate in several cancer-related pathways. The increased expression level of KIF15 was correlated with worse clinical outcomes in many types of human cancers. Additionally, KIF15 expression was related to cancer infiltration of immune cells, tumor mutation burden, and microsatellite instability. In the analysis of NPC, KIF15 was significantly upregulated based on the GEO database and immunohistochemistry. A high expression of KIF15 was negatively associated with the prognosis of patients with NPC. A nomogram model integrating clinical characteristics and KIF15 expression was established, and it showed good predictive ability with an area under the curve value of 0.73. KIF15 knockdown significantly inhibited NPC cell proliferation and migration.ConclusionsOur findings revealed the important and functional role of KIF15 as an oncogene in pan-cancer. Moreover, high expression of KIF15 was found in NPC tissues, and was correlated with poor prognosis in NPC. KIF15 may serve as a potential therapeutic target in NPC treatment.

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“…Kif15 may also have uncharacterized roles in other aspects of kinetochore-microtubule attachment, suggested by data showing that overexpression of Kif15 results in lagging chromosomes (Malaby et al, 2019). In this light, it is notable that Kif15 is upregulated in a number of cancers (Ma et al, 2014;Wang et al, 2017;Qiao et al, 2018;Yu et al, 2019;Zhao et al, 2019;Sun et al, 2020;Terribas et al, 2020). Under normal circumstances, however, Kif15 localizes predominantly to k-fiber microtubules.…”

Section: Introductionmentioning

confidence: 99%

K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15

Begley

Solon

Davis

et al. 2021

MBoC

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The mitotic spindle, a self-constructed microtubule-based machine, segregates chromosomes during cell division. In mammalian cells, microtubule bundles called kinetochore-fibers (k-fibers) connect chromosomes to the spindle poles. Chromosome segregation thus depends on the mechanical integrity of k-fibers. Here, we investigate the physical and molecular basis of k-fiber bundle cohesion. We detach k-fibers from poles by laser ablation-based cutting, thus revealing the contribution of pole-localized forces to k-fiber cohesion. We then measure the physical response of the remaining kinetochore-bound segments of the k-fibers. We observe that microtubules within ablated k-fibers often splay apart from their minus-ends. Furthermore, we find that minus-end clustering forces induced by ablation seem at least partially responsible for k-fiber splaying. We also investigate the role of the k-fiber-binding kinesin-12 Kif15. We find that pharmacological inhibition of Kif15-microtubule binding reduces the mechanical integrity of k-fibers. In contrast, inhibition of its motor activity but not its microtubule binding ability, i.e., locking Kif15 into a rigor state, does not greatly affect splaying. Altogether, the data suggest that forces holding k-fibers together are of similar magnitude to other spindle forces, and that Kif15, acting as a microtubule crosslinker, helps fortify and repair k-fibers. This feature of Kif15 may help support robust k-fiber function and prevent chromosome segregation errors. [Media: see text] [Media: see text] [Media: see text]

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KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma

Cited by 10 publications

References 35 publications

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

Integrative Pan-Cancer Analysis of KIF15 Reveals Its Diagnosis and Prognosis Value in Nasopharyngeal Carcinoma

K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15

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