Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

Ward, Alejandra; Morettin, Alan; Shum, David; Hudson, John W.

doi:10.1186/1471-2407-11-71

Cited by 18 publications

(21 citation statements)

References 40 publications

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“…A previous study showed that both mRNA and protein expressions of PLK4 gradually decreased from normal liver to HCC [24]. In this study, to elucidate the clinical role of PLK4 in HCC, we applied TMA and IHC to examine its expression in a cohort of Chinese patients.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Polo-Like Kinase 4 in Hepatocellular Carcinoma Associates with Poor Prognosis

et al. 2012

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Polo-like kinase 4 (PLK4), belonging to serine/threonine kinase family, is critical for centriole replication and cell cycle progression. PLK4 has been proposed as a tumor suppressor in hepatocellular carcinoma (HCC). However, its expression and significance in HCC have not been well studied. In the present study, we found that PLK4 was markedly downregulated in both HCC cell lines and fresh cancer tissues, using quantitative real-time-PCR and western blot. Immunohistochemistry data also revealed that decreased expression of PLK4 was present in 72.4% (178/246) of HCC tissues, compared with the corresponding adjacent nontumorous tissues. Furthermore, PLK4 expression significantly correlated with clinicopathological parameters, including clinical stage (P = 0.034), serum α-fetoprotein (AFP) (P = 0.019) and tumor size (P = 0.032). Moreover, HCC patients with low PLK4 expression survived shorter than those with high PLK4 expression, as indicated by overall survival (P = 0.002) and disease-free survival (P = 0.012) assessed by the Kaplan–Meier method. In addition, multivariate analysis suggested PLK4 as an independent predictor of overall survival (HR, 0.556; 95%CI, 0.376−0.822; P = 0.003) and disease-free survival (HR, 0.547; 95%CI, 0.382−0.783; P = 0.001). Collectively, our study demonstrated that PLK4 was remarkably downregulated in HCC and could be served as a potential prognostic marker for patients with this deadly disease.

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Section: Discussionmentioning

confidence: 99%

Downregulation of Polo-Like Kinase 4 in Hepatocellular Carcinoma Associates with Poor Prognosis

et al. 2012

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“…Deregulation of PLK1 expression has also been associated with hypomethylation at the promoter region of PLK1 gene. Hypomethylation of PLK1 promoter has been observed in mouse hepatocellular carcinoma53 54 and human haematological malignancies 55. The loss of methylation correlated (75.7% in haematological malignancies) with elevated PLK1 expression in tumour cells.…”

Section: Plk1 and Oncogenesismentioning

confidence: 96%

Molecular interactions of polo-like kinase 1 in human cancers

et al. 2016

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Polo-like kinase 1 (PLK1) is an essential protein in communicating cell-cycle progression and DNA damage. Overexpression of PLK1 has been validated as a marker for poor prognosis in many cancers. PLK1 knockdown decreases the survival of cancer cells. PLK1 is therefore an attractive target for anticancer treatments. Several inhibitors have been developed, and some have been clinically tested to show additive effects with conventional therapies. Upstream regulation of PLK1 involves multiple interactions of proteins such as FoxM1, E2F and p21. Other cancer-related proteins such as pRB and p53 also indirectly influence PLK1 expression. With the high mutation rates of these genes seen in cancers, they may be associated with PLK1 deregulation. This raises the question of whether PLK1 overexpression is a cause or a consequence of oncogenesis. In addition, hypomethylation of the CpG island of the PLK1 promoter region contributes to its upregulation. PLK1 expression can be affected by many factors; thus, it is possible that PLK1 deregulation in each individual patient tumours could be due to different underlying mechanisms.

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“…PLK4 acts as a tumor suppressor in hepatocellular carcinoma (HCC). 100 PLK4 production is reduced during hepatic carcinogenesis by promoter hypermethylation 101 and might contribute to HCC development in infertile men who carry a mutation in PLK4. 98,102 103 It regulates homologous chromosome synapsis and double-strand DNA breakage repair.…”

Section: Plk4 and Sertoli-cell-only Syndromementioning

confidence: 99%

Human male infertility and its genetic causes

Miyamoto

Minase

Shin

et al. 2017

Reprod Medicine & Biology

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BackgroundInfertility affects about 15% of couples who wish to have children and half of these cases are associated with male factors. Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations/deletions of several Y chromosome genes. Many researchers have analyzed genes in the AZF region on the Y chromosome; however, in 2003 the SYCP3 gene on chromosome 12 (12q23) was identified as causing azoospermia by meiotic arrest through a point mutation.MethodsWe mainly describe the SYCP3 and PLK4 genes that we have studied in our laboratory, and add comments on other genes associated with human male infertility.ResultsUp to now, The 17 genes causing male infertility by their mutation have been reported in human.ConclusionsInfertility caused by nonobstructive azoospermia (NOA) is very important in the field of assisted reproductive technology. Even with the aid of chromosomal analysis, ultrasonography of the testis, and detailed endocrinology, only MD‐TESE can confirm the presence of immature spermatozoa in the testes. We strongly hope that these studies help clinics avoid ineffective MD‐TESE procedures.

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Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

Cited by 18 publications

References 40 publications

Downregulation of Polo-Like Kinase 4 in Hepatocellular Carcinoma Associates with Poor Prognosis

Downregulation of Polo-Like Kinase 4 in Hepatocellular Carcinoma Associates with Poor Prognosis

Molecular interactions of polo-like kinase 1 in human cancers

Human male infertility and its genetic causes

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