Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq

Ouyang, Yueping; Pan, Juncheng; Tai, Qiang; Ju, Jingfang; Wang, Huaizhi

doi:10.1007/s13277-015-4379-x

Cited by 15 publications

(25 citation statements)

References 48 publications

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“…Recently, Hirata H et al also found that DKK4 could activate JNK pathway while inhibiting β-catenin signaling in renal cell carcinoma [18]. Ouyang et al found that DKK4 might promote the development of pancreatic cancer through the abnormal activation of MAPK3 pathway [17]. In this report, our results found that DKK4 could promote c-jun and JNK protein phosphration, indicating DKK4 could promote invasion through activating JNK pathway.…”

Section: Discussionsupporting

confidence: 62%

“…A larger number of samples needed to be analyzed to testify our results. Although DKK4 overexpression was found in some cancers, like, colon [15, 16, 31], pancreatic [17], and renal cancer [18], limited information was available on the role of DKK4 protein in predicting cancer prognosis. In this report, our results showed that elevated DKK4 protein expression was correlated with poor prognosis for EOC patients.…”

Section: Discussionmentioning

confidence: 99%

“…However, DKK4, induced by β-catenin activation, was found to be upregulated and promote invasion and angiogenesis in human colon cancers [15, 16]. DKK4 was co-overexpressed with MAPK3 and VAV3 in pancreatic ductal adenocarcinoma tissues [17]. DKK4 could also promote cell proliferation, invasion, and migration by activating the noncanonical c-Jun-NH2 kinase signaling pathway in renal cancer [18].…”

Section: Introductionmentioning

confidence: 99%

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Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion

Wang¹,

Wei²,

Zhang³

2017

BMC Cancer

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BackgroundDickkopf-4 (DKK4), a member of DKK family, appears to be a divergent protein. It remained multi-biological functions in carcinogenesis. The effect of DKK4 on the ovarian cancer cells remains unclear. This study detected the clinical significance of DKK4 in epithelial ovarian cancer (EOC) patients and its role in invasion.MethodsQRT-PCR and western blot analysis were used to examine the levels of DKK4 mRNA and protein in 33 EOC tissues and 33 benign ovarian tumors. Immunohistochemical analysis was performed to assess DKK4 expression in 239 EOC samples. siRNA-mediated DKK4 silence was conducted. Transwell assay was used to detect the invasive ability. Phalloidin was used to stain the formations of actin filaments.ResultsThe expressions of DKK4 mRNA and protein were elevated in EOC tissues as compared with those in benign ovarian tumors (p = 0.001 and <0.0001 respectively). Immunohistochemical results showed the strong expression of DKK4 protein was positively associated with late FIGO stage (p = 0.005) and poor disease free survival in univariate and multivariate analysis (p < 0.0001 and p = 0.001, respectively). SiRNA-mediated DKK4 knockdown inhibited cell invasive ability (all p < 0.0001) and the formations of actin filaments. DKK4 could promote the phosphration of c-JUN and JNK (p < 0.0001 and p = 0.001, respectively).ConclusionsOur results indicated that DKK4 might be contributed to predicting EOC progression and prognosis. DKK4 could promote the invasion of EOC through JNK activation.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion

Wang¹,

Wei²,

Zhang³

2017

BMC Cancer

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“…Data obtained from clinical samples suggested that overexpression of this molecule is significantly associated with the progression and prognosis of certain cancers, and functional assays demonstrated that PIK3R3 could promote the proliferation, migration, and invasion of some cancers in vitro and vivo [17-19]. Some studies have mentioned the role of PIK3R3 in PC [20, 21]. However, the function and mechanism of PIK3R3 in PC is still unclear, especially the function of PIK3R3 in tumor metastasis.…”

Section: Introductionmentioning

confidence: 99%

PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

Peng

Zhu

Yin

et al. 2018

Cell Physiol Biochem

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Background/Aims: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. Methods: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. Results: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. Conclusion: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.

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“…Transcriptome sequencing is used to study transcripts of particular tissues or organs of a species in a particular state and is superior to microarrays in terms of information volume and accuracy [ 12 ]. By constructing a transcriptome library, we can obtain information about transcripts and alternative splicing and can determine the differential expression patterns of specific genes [ 13 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cutaneous transcriptome analysis in NIH hairless mice

Chen

Zhang

et al. 2017

PLoS ONE

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Mice with spontaneous coat mutations are ideal animal models for studying skin development and tumorigenesis. In this study, skin hair growth cycle abnormalities were examined in NIH hairless mice 42 days after birth (P42) by using hematoxylin-eosin (H&E) staining. To examine the gene expression patterns in the skin of mutant mice, the dorsal skin of P42 female NIH mice and NIH hairless mice was sequenced by RNA-Seq, and 5,068 differentially expressed genes (DEGs) were identified (false discovery rate [FDR] ≥ 2, P < 0.05). A pathway analysis showed that basal cell carcinoma, the cell cycle and the Hippo, Hedgehog and Wnt signaling pathways were up-regulated in NIH hairless mice. Previous studies have shown that these pathways are closely associated with cell proliferation, cell cycle, organ size and cancer development. In contrast, signal transduction, bacterial and parasitic infection, and receptor-mediated pathways, including calcium signaling, were down-regulated in NIH hairless mice. A gene interaction network analysis was performed to identify genes related to hair follicle development. To verify the reliability of the RNA-Seq results, we used q-PCR to analyze 12 key genes identified from the gene interaction network analysis, including eight down-regulated and four up-regulated genes, and the results confirmed the reliability of the RNA-Seq results. Finally, we constructed the differential gene expression profiles of mutant mice by RNA-Seq. NIH hairless mice exhibited abnormalities in hair development and immune-related pathways. Pik3r1 and Pik3r3 were identified as key genes, laying the foundation for additional in-depth studies of hairless mice.

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Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq

Cited by 15 publications

References 48 publications

Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion

Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion

PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

Cutaneous transcriptome analysis in NIH hairless mice

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