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Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer

ABSTRACT: Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer

PROVIDER: PRJNA624895 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11539308.fastq.gz	Fastqsanger.gz
	SRR11539309.fastq.gz	Fastqsanger.gz
	SRR11539310.fastq.gz	Fastqsanger.gz
	SRR11539311.fastq.gz	Fastqsanger.gz
	SRR11539312.fastq.gz	Fastqsanger.gz

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Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer

Project description:We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer. Furthermore, we provided evidence that NEK2-depleted cervical cancer cells exhibit impaired oncogenesis and enhanced radiosensitivity. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression. Taken together, these results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.

2021-04-30 | GSE148531 | GEO

Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer.

Project description:BackgroundNEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown.MethodsWe detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR.ResultsWe report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression.ConclusionsOur results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.

| S-EPMC7488040 | biostudies-literature

NEK2 regulates triple negative breast cancer transcriptome.

Project description:NEK2 is a mitotic kinase that is upregulated and mislocalized in the nucleus of human cancer cells. NEK2 modulates expression and activity of both transcription and splicing factors in cancer cells, nevertheless whether this kinase affects transcriptome regulation genome widely and whether this activity concurs to its oncogenic activity is still unknown. Herein, by high-throughput RNA sequencing analysis of MDA-MB-231 cells transiently silenced for NEK2 we uncover an extensive modulation of triple-negative breast cancer cell transcriptome by this kinase.

2021-12-21 | GSE140803 | GEO

Effect of NEK2 deficiency on gene expression of CD19-selected spleen B cells of Eμ-myc mouse model

Project description:NEK2 overexpression in the B cell lineage affects B cell development. To determine whether deficiency of NEK2 inhibits B cell malignancies, we crossed Nek2 knockout mice with Eμ-myc transgenic mice, a well-established Myc-driven preclinical model for B cell malignancies. Three genotyping offsprings were obtained: Eμ-myc/Nek2+/+ (NEK2 wild type), Eμ-myc/Nek2+/- (NEK2 heterozygotes), and Eμ-myc/Nek2-/- (NEK2 homozygotes). Bulk RNA-seq was performed on CD19-selected spleen B cells to view the transcriptome differences.

2023-06-01 | GSE226675 | GEO

LC-MS proteomics quantitative analysis of pancreatic cancer cells overexpressing NEK2

Project description:The NEK2 overexpression in pancreactic cancer cell (SW1990), and we performed LC-MS to further investigate the manner in which NEK2 regulates PD-L1.

2021-06-29 | PXD026877 | Pride

Expression Data from ST2 cells treated with Wnt1

Project description:Wnt1 has major anabolic functions in bone metabolism. We investigated the effect of recombinant murine Wnt1/Sfrp1 complex on the mesenchymal cell line ST2. We used microarray analysis to detail the global gene expression of ST2 cells in response to 6 hour of treatment with 100 ng recombinant Wnt1/Sfrp1 complex.

2022-08-17 | GSE211391 | GEO

Multi-Omic analyses reveal aberrant differentiation trajectory with WNT1 Loss-of-Function in type XV osteogenesis imperfecta

Project description:Osteogenesis imperfecta (OI) is a serious genetic bone disorder characterized by congenital low bone mass, deformity and frequent fractures. Type XV OI is a moderate to severe form of skeletal dysplasia caused by WNT1 mutations. In this cohort study from southern China, we summarized the clinical phenotypes of patients with WNT1 mutations and found the proportion of type XV patients was around 10.3% (25 out of 243) with diverse phenotypic spectrums. Functional assays indicated that mutations of WNT1 significantly impaired its secretion and effective activity, leading to moderate to severe clinical manifestations, porous bone structure and enhanced osteoclastic activities. Analysis of proteomic data from human skeleton indicated that the expression of SOST was dramatically reduced in type XV patients. Single-cell transcriptome data generated from human tibia samples revealed aberrant differentiation trajectory of skeletal progenitors and impaired maturation of osteocytes, resulting in excessive CXCL12+ progenitors and abnormal cell populations with adipogenic characteristics. The integration of multi-omics data from human skeleton delineates how WNT1 regulates the differentiation and maturation of skeletal progenitors, which will provide a new direction for the treatment strategy of type XV osteogenesis imperfecta and relative low bone mass diseases such as early onset osteoporosis.

2024-10-17 | PXD050841 | Pride

bulk RNA-seq of wild-type, Gli2f/f;Gli3f/f;Wnt1-Cre, and Hand2f/f;Wnt1-Cre mouse e10.5 dissection mandibular prominences

Project description:bulk RNA-seq of wild-type, Gli2f/f;Gli3f/f;Wnt1-Cre, and Hand2f/f;Wnt1-Cre mouse e10.5 dissection mandibular prominences

2020-10-01 | GSE141431 | GEO

Expression Data from ST2 cells transfected with a Wnt1 expressing plasmid

Project description:Wnt1 has major anabolic functions in bone metabolism. We investigated the effect of of Wnt1 on the mesenchymal cell line ST2 by transfecting it with a pLNCX-Wnt1 expression plasmid. We used microarray analysis to detail the global gene expression of ST2 cells 5 days after transfection with 1 µg pLNCX-Wnt1.

2024-08-14 | GSE249300 | GEO

Gene expression profile at single cell level of bone marrow cells in 5TGM1 multiple myeloma mouse model of NEK2 deficiency

Project description:To determine how the lack of NEK2 in the tumor microenvironmental cells contributes to tumor inhibition and immune regulation, we used single cell RNA sequencing (scRNA-seq) to analyze the diversity of immune cells in the bone marrow of 5TGM1 MM mouse model with and without NEK2 deficiency.

2023-06-01 | GSE226697 | GEO

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