Short communication: A splice site mutation in CENPU is associated with recessive embryonic lethality in Holstein cattle

Hozé, Chris; Escouflaire, Clémentine; Uddin, Md Mesbah; Barbat, Anne; Boussaha, Mekki; Deloche, Marie-Christine; Boichard, Didier; Fritz, Sébastien; Capitan, Aurélien

doi:10.3168/jds.2019-17056

Cited by 24 publications

(10 citation statements)

References 20 publications

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“…For one, CENP-U is a part of the kinetochore, and its deficiency was reported to lead to embryonic lethality in mice and Holstein cattle. Additionally, disrupted CENP-U expression of mouse ES cells was found to result in the disappearance of all CENP-O class proteins and ultimately mitotic defects (10,11), further demonstrating the importance of CENP-U in mitosis. Moreover, PBIP1 (CENP-U) is essential for recruiting polo-like kinase 1 (PLK1) to the kinetochore and may be the sole receptor of PLK1 in core kinetochore, which is crucial for promoting centrosome maturation and spindle assembly (12,13).…”

Section: Introductionmentioning

confidence: 91%

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Shao¹,

Wang²,

Duan³

et al. 2021

Ann Transl Med

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Background: Centromere protein U (CENP-U) is a component of the kinetochore and can regulate the cell cycle as a receptor of polo-like kinase 1 (PLK1). Recent studies have partially identified the role of CENP-U in tumor progression, but the underlying mechanisms of CENP-U in tumor immunity remain obscure. Methods: We performed pan-cancer analysis to evaluate the role of CENP-U in immunity and proliferation with data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE) datasets, and Genotype-Tissue Expression (GTEx) project. Results of CENP-U expression and related clinicopathological data were obtained to show the expression levels, prognosis, tumor progression, immune neoantigens, and immune checkpoints of CENP-U in 33 tumors. The Tumor Immune Estimation Resource (TIMER) dataset was used to analyze immune infiltration scores.Results: Results of the pan-cancer analysis demonstrated that CENP-U is differentially expressed in normal tissues and common tumor tissues. Moreover, differentially expressed CENP-U was also identified between matched normal and tumor tissues, and the high expression level of CENP-U was associated with poor prognosis for 33 kinds of tumor except for that of thymoma (THYM) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC). Furthermore, the correlation between CENP-U expression and immune checkpoints and immune neoantigens was determined. In addition, CENP-U expression was correlated with tumor-infiltrating immune cells especially in THYM but not in lung squamous cell carcinoma (LUSC), esophageal carcinoma (ESCA), or lung adenocarcinoma (LUAD). Finally, gene set enrichment analysis (GSEA) indicated that CENP-U is critically involved in tumor proliferation, immunity, and metabolism.Conclusions: CENP-U, a mitosis-related kinase, was found to be differentially expressed across different cancer types and to play an important role in tumor progression and immunity. CENP-U holds the potential to be a prognostic marker, whose targeting may provide therapeutic benefit.

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Section: Introductionmentioning

confidence: 91%

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Shao¹,

Wang²,

Duan³

et al. 2021

Ann Transl Med

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“…CENPU localizes to human chromosome 4q35.1 and encodes a 46 kDa protein [10]. More recently, previous studies suggested that CENPU was expressed in various tissues such as a fetal liver, bone marrow, and thymus and testis [11][12][13][14][15]. Accumulating evidence has indicated that CENPU is upregulated in several human cancers and may play a key role in cancer progression [16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Centromere protein U (CENPU), also called CENP-50/ PBIP1, KLIP1, or MLF1IP, is exclusively expressed in cen-tromeres throughout the cell cycle [9][10][11][12][13][14][15]. Recently, multiple studies have suggested the aberrant expression of CENPU in various human solid tumors, such as non-small-cell lung cancer (NSCLC), bladder cancer, ovarian cancer, and breast cancer, which highlights the crucial role of CENPU in these tumors [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Expression of Centromere Protein U Is Associated with Hepatocellular Cancer Progression

Chen

Zhang

et al. 2021

BioMed Research International

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Background. Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, but its molecular mechanism is unclear. Abnormal expression of centromere protein U (CENPU) is closely related to diverse human cancers. The purpose of this article was to evaluate the function and potential mechanisms of CENPU in HCC development. Methods. We performed bioinformatics analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter databases to investigate the clinical significance and prognostic value of CENPU in HCC. Western blotting and immunohistochemical staining were used to measure protein expression, while reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was used to determine mRNA expression. Cell Counting Kit8 (CCK-8) and colony formation assays were conducted to examine cell proliferation. Transwell and wound healing assays were used to assess cell migration and invasion. Gene set enrichment analysis (GSEA) was used to explore the potential signaling pathways of CENPU involved in HCC. Results. High expression of CENPU in HCC was predicted by public database analysis and indicated a poor prognosis. CENPU expression was significantly higher in HCC tissues and cells than in normal tissues and cell. In vitro, CENPU promoted the proliferation, migration, and invasion of HCC cells. GSEA results indicated that CENPU was linked to the Notch signaling pathway, and our research supported this prediction. Conclusion. CENPU promotes the malignant biological process of HCC and may be a promising target for HCC treatment.

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“…In cattle, the original works of VanRaden et al [ 17 ] and Fritz et al [ 18 ] using reverse genetic screen followed by whole-genome sequence analyses have successfully identified candidate causal variants in linkage disequilibrium with haplotypes with significant partial or total deficit in homozygous animals. Going on with this approach, numerous embryonic lethal mutations were identified in Holstein and Jersey breeds altering APAF1 [ 19 ], SMC2 [ 20 , 21 ], GART [ 18 ], TFB1M [ 22 ], SDE2 [ 23 ], CENPU [ 24 ] and CWC15 [ 25 ] genes. Additionally, neonatal/juvenile lethal mutations associated with homozygous haplotype deficiency were also identified in Ayshire and Braunvieh breeds affecting UBE3B [ 20 ] and TUBD1 [ 26 ] genes.…”

Section: Introductionmentioning

confidence: 99%

A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep

Braiek

Moreno‐Romieux

Allain

et al. 2021

Genes

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We recently demonstrated that the Lacaune deficient homozygous haplotype 6 (LDHH6) potentially hosts a recessive perinatal lethal mutation in Lacaune dairy sheep mapped on OAR3. In the present study, we have analyzed the whole-genome sequences of two Lacaune ram heterozygous carriers of LDHH6. After variant calling and filtering against the variants of 86 non-carrier rams, we have identified a single nucleotide variant (SNV) in the two LDHH6 carriers whose variant allele induced a premature stop codon (p.Glu111*) in the Coiled-Coil Domain Containing 65 (CCDC65) gene. CCDC65 is involved in the assembly of the nexin-dynein regulatory complex for the formation of microtubules in ciliated cells. In order to identify the phenotype in homozygous sheep, we generated at-risk matings (n = 17) between rams and ewes heterozygous for the candidate variant in CCDC65. A total of 16 lambs were born alive with five genotyped as homozygous carriers. The homozygous lambs suffered from respiratory problems, and four of them died within the first month of life. At necropsy, we observed a broad hepatization of lung lobes possibly induced by infectious pneumonia. The management of this lethal recessive allele (frequency of 0.06) through reasoned mating in the Lacaune sheep selection schemes could reduce lamb mortality by 2%.

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Short communication: A splice site mutation in CENPU is associated with recessive embryonic lethality in Holstein cattle

Cited by 24 publications

References 20 publications

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Abnormal Expression of Centromere Protein U Is Associated with Hepatocellular Cancer Progression

A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep

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