Cyclin-Dependent Kinase 14 Promotes Cell Proliferation, Migration and Invasion in Ovarian Cancer by Inhibiting Wnt Signaling Pathway

Ouyang, Jun; Huang, Lihong; Sun, Xiangxiu

doi:10.1159/000447632

Cited by 33 publications

(18 citation statements)

References 20 publications

(26 reference statements)

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“…Even though sufficient sensitivity and specificity cannot be obtained solely by immunohistochemical examination, in a clinical setting, such examination using formalin-fixed paraffin-embedded tissue specimens of surgically resected material would be an auxiliary procedure for ER risk diagnosis based on quantification of DNA methylation. CDK14 reportedly participates in the proliferation and invasion of many tumor cells, including those of breast cancer (Imawari et al 2018), glioma (Fan et al 2015), hepatocellular carcinoma (Tu et al 2019), and ovarian cancer (Ou-Yang et al 2017). In pancreatic cancers, CDK14 has been revealed as a hub gene in the interaction network including the Wnt/β-catenin pathway and phosphoinositide 3-kinase/Akt signaling pathway, and its increased expression is associated with poorer overall patient survival (Yuan et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling

Endo

Fujimoto

Ito

et al. 2021

J Cancer Res Clin Oncol

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Purpose The present study was conducted to clarify the clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma (PDAC). Methods Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analyzed fresh-frozen tissues from an initial cohort (17 samples of normal control pancreatic tissue [C] from 17 patients without PDAC, and 34 samples of non-cancerous pancreatic tissue [N] and 82 samples of cancerous tissue [T] both obtained from 82 PDAC patients) and formalin-fixed paraffin-embedded T samples from 34 patients in a validation cohort. Results The DNA methylation profiles of N samples tended to differ from those of C samples, and 91,907 probes showed significant differences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was significantly correlated with a larger tumor diameter and early recurrence (ER), defined as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fixed paraffin-embedded surgically resected materials regardless of their tumor cell content, were identified for prediction of ER. The sensitivity and specificity for detection of patients belonging to the ER group using a panel combining these three marker CpG sites, including a CpG site in the CDK14 gene, were 81.8% and 71.7% and 88.9% and 70.4% in the initial and validation cohorts, respectively. Conclusion These findings indicate that DNA methylation alterations may have a clinicopathological impact on PDAC. Application of our criteria will ultimately allow prediction of ER after surgery to improve the outcome of PDAC patients.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling

Endo

Fujimoto

Ito

et al. 2021

J Cancer Res Clin Oncol

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“…A previous study indicated that cyclin Y and CDK14 could interact at the membrane to modulate LRP6 activation through phosphorylation [59]. Notably, the expression of CDK14 was also upregulated in clinical EOC samples and its expression was found to enhance the accumulation of nuclear β-catenin [60]. Therefore, the upregulation and association of cyclin Y and CDK14 in EOC may promote canonical Wnt signalling.…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis

et al. 2019

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Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The Wnt/β-catenin pathway plays critical roles in regulating embryonic development and physiological processes. This pathway is tightly regulated to ensure its proper activity. In the absence of Wnt ligands, β-catenin is degraded by a destruction complex. When the pathway is stimulated by a Wnt ligand, β-catenin dissociates from the destruction complex and translocates into the nucleus where it interacts with TCF/LEF transcription factors to regulate target gene expression. Aberrant activation of this pathway, which leads to the hyperactivity of β-catenin, has been reported in ovarian cancer. Specifically, mutations of CTNNB1, AXIN, or APC, have been observed in the endometrioid and mucinous subtypes of EOC. In addition, upregulation of the ligands, abnormal activation of the receptors or intracellular mediators, disruption of the βcatenin destruction complex, inhibition of the association of β-catenin/E-cadherin on the cell membrane, and aberrant promotion of the β-catenin/TCF transcriptional activity, have all been reported in EOC, especially in the high grade serous subtype. Furthermore, several non-coding RNAs have been shown to regulate EOC development, in part, through the modulation of Wnt/β-catenin signalling. The Wnt/β-catenin pathway has been reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC. Emerging evidence also suggests that the pathway induces ovarian tumor angiogenesis and immune evasion. Taken together, these studies demonstrate that the Wnt/β-catenin pathway plays critical roles in EOC development and is a strong candidate for the development of targeted therapies.

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“…In glioma, the level of miR-128-3p expression was dramatically attenuated in glioma clinical tissues, and miR-128-3p regulated the progression of glioma via targeting NPTX1 and activating the IRS-1/PI3K/ AKT signaling pathway [12]. Cyclin-dependent kinase 14 (CDK14) is a member of cyclin-dependent kinases, and a previous study demonstrated that CDK14 was augmented in the tissues and cells of OC [13].…”

Section: Introductionmentioning

confidence: 99%

LncRNA MIR4435-2HG triggers ovarian cancer progression by regulating miR-128-3p/CKD14 axis

et al. 2020

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Background: Accumulating studies showed that long noncoding RNAs (lncRNAs) played vital roles in cancer progression. LncRNA MIR4435-2HG was proved to act as an oncogene in various tumors. However, the underlying function of MIR4435-2HG in ovarian cancer (OC) remains unclear. Methods: The expression levels of MIR4435-2HG, miR-128-3p and cyclin-dependent kinase 14 (CDK14) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis in OC cells were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis, respectively. Transwell assay was applied to evaluate cell migration and invasion. Wound healing assay was performed to monitor the migration rate. Western blot assay was performed to detect the protein levels of Bcl-2, Cleaved PARP, E-cadherin, Vimentin and CDK14 in OC cells. The binding sites between miR-128-3p and MIR4435-2HG or CDK14 were predicted by online tool starBase and their relationship was confirmed by dual-luciferase reporter assay, RIP assay and pull-down experiment. Results: MIR4435-2HG and CDK14 were over-expressed in OC tissues and cells. Patients with high MIR4435-2HG expression had poorer overall survival (OS) than patients with low MIR4435-2HG expression. MIR4435-2HG knockdown inhibited proliferation, invasion and migration but induced apoptosis of OC cells via miR-128-3p/CDK14 axis. In conclusion, MIR4435-2HG knockdown suppressed the progression of OC cells through downregulating CDK14 expression by the promotion of miR-128-3p.

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Cyclin-Dependent Kinase 14 Promotes Cell Proliferation, Migration and Invasion in Ovarian Cancer by Inhibiting Wnt Signaling Pathway

Cited by 33 publications

References 20 publications

Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling

Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling

Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis

LncRNA MIR4435-2HG triggers ovarian cancer progression by regulating miR-128-3p/CKD14 axis

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