Kif18a regulates Sirt2-mediated tubulin acetylation for spindle organization during mouse oocyte meiosis

Tang, Feng; Pan, Meng-Hao; Wan, Xiang; Lu, Yujie; Sun, Shao‐Chen

doi:10.1186/s13008-018-0042-4

Cited by 22 publications

(11 citation statements)

References 41 publications

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“…Meanwhile, KIF18A belongs to the kinesin 9 family. It has a significantly upregulated expression in G2/M phase, which can contribute to the arrangement of chromosomes on the equatorial plate by adjusting the length of microtubules (Mts), ensuring the normal separation of sister chromosomes and normal progression of mitosis ( 48 – 51 ). High expression of KIF18A has been confirmed in multiple cancers such as breast cancer, lung cancer, and colorectal cancer ( 52 – 54 ).…”

Section: Discussionmentioning

confidence: 99%

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Teng

Zhu

et al. 2022

Front. Immunol.

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Despite a generally better prognosis than high-grade glioma (HGG), recurrence and malignant progression are the main causes for the poor prognosis and difficulties in the treatment of low-grade glioma (LGG). It is of great importance to learn about the risk factors and underlying mechanisms of LGG recurrence and progression. In this study, the transcriptome characteristics of four groups, namely, normal brain tissue and recurrent LGG (rLGG), normal brain tissue and secondary glioblastoma (sGBM), primary LGG (pLGG) and rLGG, and pLGG and sGBM, were compared using Chinese Glioma Genome Atlas (CGGA) and Genotype-Tissue Expression Project (GTEx) databases. In this study, 296 downregulated and 396 upregulated differentially expressed genes (DEGs) with high consensus were screened out. Univariate Cox regression analysis of data from The Cancer Genome Atlas (TCGA) yielded 86 prognostically relevant DEGs; a prognostic prediction model based on five key genes (HOXA1, KIF18A, FAM133A, HGF, and MN1) was established using the least absolute shrinkage and selection operator (LASSO) regression dimensionality reduction and multivariate Cox regression analysis. LGG was divided into high- and low-risk groups using this prediction model. Gene Set Enrichment Analysis (GSEA) revealed that signaling pathway differences in the high- and low-risk groups were mainly seen in tumor immune regulation and DNA damage-related cell cycle checkpoints. Furthermore, the infiltration of immune cells in the high- and low-risk groups was analyzed, which indicated a stronger infiltration of immune cells in the high-risk group than that in the low-risk group, suggesting that an immune microenvironment more conducive to tumor growth emerged due to the interaction between tumor and immune cells. The tumor mutational burden and tumor methylation burden in the high- and low-risk groups were also analyzed, which indicated higher gene mutation burden and lower DNA methylation level in the high-risk group, suggesting that with the accumulation of genomic mutations and epigenetic changes, tumor cells continued to evolve and led to the progression of LGG to HGG. Finally, the value of potential therapeutic targets for the five key genes was analyzed, and findings demonstrated that KIF18A was the gene most likely to be a potential therapeutic target. In conclusion, the prediction model based on these five key genes can better identify the high- and low-risk groups of LGG and lay a solid foundation for evaluating the risk of LGG recurrence and malignant progression.

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Section: Discussionmentioning

confidence: 99%

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Teng

Zhu

et al. 2022

Front. Immunol.

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“…Inhibition of different histone deacetylases such as HDAC3, HDAC6, and HDAC11 all could cause spindle defects in oocytes [46][47][48]. Besides, kinesins such as Kif11, Kif17, and Kif18 are shown to affect spindle organization through their effects on microtubule acetylation level during mouse oocyte maturation [49][50][51]. Our results reveal that PRC1 KD resulted in increased acetylation of microtubules in mouse oocytes, while the supplementation of PRC1 mRNA could reduce tubulin acetylation to the normal level, which further confirmed the role of PRC1 in formation of the spindle midzone in mouse oocytes.…”

Section: Discussionmentioning

confidence: 99%

PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis

Pan

et al. 2020

The FEBS Journal

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Protein regulator of cytokinesis 1 (PRC1) is a microtubule bundling protein that is involved in the regulation of the central spindle bundle and spindle orientation during mitosis. However, the functions of PRC1 during meiosis have rarely been studied. In this study, we explored the roles of PRC1 during meiosis using an oocyte model. Our results found that PRC1 was expressed at all stages of mouse oocyte meiosis, and PRC1 accumulated in the midzone/midbody during anaphase/telophase I. Moreover, depleting PRC1 caused defects in polar body extrusion during mouse oocyte maturation. Further analysis found that PRC1 knockdown did not affect meiotic spindle formation or chromosome segregation; however, deleting PRC1 prevented formation of the midzone and midbody at the anaphase/telophase stage of meiosis I, which caused cytokinesis defects and further induced the formation of two spindles in the oocytes. PRC1 knockdown increased the level of tubulin acetylation, indicating that microtubule stability was affected. Furthermore, KIF4A and PRC1 showed similar localization in the midzone/midbody of oocytes at anaphase/telophase I, while the depletion of KIF4A affected the expression and localization of PRC1. The PRC1 mRNA injection rescued the defects caused by PRC1 knockdown in oocytes. In summary, our results suggest that PRC1 is critical for midzone/midbody formation and cytokinesis under regulation of KIF4A in mouse oocytes.

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“…Furthermore, in fission yeast, a homolog of human splicing factor RBM10 was associated with the histone deacetylase Clr6 complex and facilitated heterochromatin assembly (Weigt et al, 2020). Based on these data, we speculate that RBM14 might interact with the histone deacetylase family proteins, such as HDAC3 or Sirt2, which has been reported to regulate microtubule stability and spindle organization through deacetylating α-tubulin (Li et al, 2017;Tang et al, 2018b). Hence, we cannot rule out the possibility that RBM14 could modulate histone deacetylase activities and form a tripartite protein complex with α-tubulin to co-regulate the acetylation of α-tubulin.…”

Section: Discussionmentioning

confidence: 79%

RBM14 Modulates Tubulin Acetylation and Regulates Spindle Morphology During Meiotic Maturation in Mouse Oocytes

Qin

Yuan

et al. 2021

Front. Cell Dev. Biol.

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RBM14 is an RNA-binding protein that regulates spindle integrity in mitosis; however, its functions during meiosis are still unclear. In this study, we discovered that RBM14 expression was down-regulated in oocytes from old mice. The RBM14 distribution at different stages of meiosis was explored, while it presents overlapped localization patterns with α-tubulin in MI- and MII-stage oocytes. Treatment of MI-stage oocytes with spindle-perturbing agents revealed that RBM14 was co-localized with microtubules. RBM14 knockdown with RBM14-specific morpholino showed that RBM14-depleted oocytes underwent symmetric division compared to the controls. RBM14 knockdown also resulted in spindle defects and chromosome abnormalities during oocyte maturation, presumably due to α-tubulin hyperacetylation. Co-immunoprecipitation analysis demonstrated that RBM14 is interacted with endogenous α-tubulin in mammalian cells. These findings indicate that RBM14 is an essential modulator of oocyte meiotic maturation by regulating α-tubulin acetylation to affect spindle morphology and chromosome alignment. Consequently, RBM14 represents a potential biomarker of oocyte quality and a novel therapeutic target in women with oocyte maturation failure.

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Kif18a regulates Sirt2-mediated tubulin acetylation for spindle organization during mouse oocyte meiosis

Cited by 22 publications

References 41 publications

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis

RBM14 Modulates Tubulin Acetylation and Regulates Spindle Morphology During Meiotic Maturation in Mouse Oocytes

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