The constitutively active PKG II mutant effectively inhibits gastric cancer development <i>via</i> a blockade of EGF/EGFR-associated signalling cascades

Wu, Yan; Yuan, Miaomiao; Su, Wen-Bin; Zhu, Mengyi; Yao, Xiaoyuan; Wang, Ying; Qian, Hai; Jiang, Lu; Yan, Tao; Wu, Min; Pang, Ji; Chen, Yongchang

doi:10.1177/1758834017751635

Cited by 17 publications

(13 citation statements)

References 41 publications

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“…Our results also confirmed that l -Arg-triggered PKG II activation blocked Raf/MEK and PI3K/Akt signaling pathways. Furthermore, the activated PKG II could also inhibit the upstream protein EGFR activation which is consistent with previous results [37]. All these data further confirm the inhibitory effect of activated PKG II on OC cells, indicating that PKG II maybe an anti-cancer factor with extensive effects.…”

Section: Discussionsupporting

confidence: 92%

Active PKG II inhibited the growth and migration of ovarian cancer cells through blocking Raf/MEK and PI3K/Akt signaling pathways

Cai

et al. 2019

Bioscience Reports

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Despite advances in chemotherapy, ovarian cancer (OC) is still the most lethal gynecologic malignancy. So, it is imperative to explore its mechanism and find novel targets to improve the outcome. Type II cyclic guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG II) has been recently reported to inhibit proliferation and metastasis in several tumors. The present study is to clarify the effect of PKG II combined with l-arginine (l-Arg) on OC cells. SKOV3 and A2780 cells were infected with adenovirus coding cDNA of PKG II to increase PKG II expression and l-Arg was applied to activate this kinase. CCK8 assay, Transwell migration and TUNEL assay were applied to detect the proliferation, migration and apoptosis of the OC cells, respectively. Western blotting was used to detect the level of total and phosphorylated proteins. Our results showed that co-treatment with PKG II and l-Arg inhibited EGF-induced proliferation and the expression of Proliferating Cell Nuclear Antigen (PCNA), Cyclin E and N-Cadherin, whereas up-regulated the expression of E-Cadherin, abolished the anti-apoptotic effect of EGF, prevented the process of epithelial-to-mesenchymal transition (EMT) as well as blocked EGF-triggered Raf-MEK and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Our results suggested that PKG II activated by l-Arg could inhibit proliferation and migration and promote the apoptosis of OC cells. Based on the above results and our previous data, it is speculated that PKG II is an inhibitor of cancer with extensive effects.

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Section: Discussionsupporting

confidence: 92%

Active PKG II inhibited the growth and migration of ovarian cancer cells through blocking Raf/MEK and PI3K/Akt signaling pathways

Cai

et al. 2019

Bioscience Reports

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“…Most of these DEmRNAs are closely associated with carcinogenesis and progression, for example CCND1, 61 VIM, 62 and EGF. 63 Specifically, CCND1 and EGF were identified as the main genes, and enriched in multiple pathways associated with cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction and comprehensive analysis of dysregulated long non‐coding RNA‐associated competing endogenous RNA network in clear cell renal cell carcinoma

Wang

Zhang

et al. 2018

J of Cellular Biochemistry

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Objective This study aimed to assess the long noncoding RNA (lncRNA)‐microRNA (miRNA)‐messenger RNA (mRNA) regulatory network in clear cell renal cell carcinoma (ccRCC) by gene expression analyses. Materials and Methods LncRNA, miRNA, and mRNA expression profiles in ccRCC were obtained from The Cancer Genome Atlas. Differentially expressed lncRNAs, mRNAs (cut‐off: |log 2 [fold change, FC])| > 2.0 and adjusted P < 0.01) and miRNAs (|log 2FC| > 1.5 and adjusted P < 0.01) were unveiled using R. Cox regression analysis was performed to identify prognostic factors of ccRCC related to overall survival (OS). A protein‐protein interaction (PPI) network was constructed for differentially expressed mRNAs (DEmRNAs) by Search Tool for the Retrieval of Interacting Genes (STRING). Key hub genes were screened from top 300 DEmRNAs. LncRNA‐miRNA and miRNA‐mRNA regulatory network were constructed and combined into the competing endogenous RNA regulatory network. Gene ontology biological terms were screened by STRING; Kyoto Encyclopedia of Genes and Genomes pathways were identified using the “clusterProfiler” package in R. Results A total of 2331, 1517, and 83 DEmRNAs, lncRNAs, and miRNAs were identified, respectively. Eleven lncRNAs (AC016773.1, HOTTIP, LINC00460, NALCN‐AS1, PVT1, TRIM36‐IT1, WT1‐AS, COL18A1‐AS1, LINC00443, LINC00472, and TCL6), three miRNAs (hsa‐mir‐21, hsa‐mir‐144, and hsa‐mir‐155), and three mRNAs (COL4A4, NOD2, and GOLGA8B) were associated with OS. Specifically, four lncRNAs (PVT1, LINC00472, TCL6, and WT1‐AS1) and one mRNA (Collagen Type IV Alpha 4 Chain) were verified as independent prognostic factors by Gene Expression Profiling Interactive Analysis. Eleven key hub genes were obtained by PPI analysis. “Cell adhesion molecules (CAMs),” “chemical carcinogenesis,” and “cytokine‐cytokine receptor interaction” were significantly enriched in the network. Conclusion The findings clarify the pathogenesis of ccRCC and might provide potential therapeutic targets.

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“…For instance, upregulation of EGFR leads to poor survival through the activation of angiogenesis in glioblastoma ( 25 ). Effective inhibition of EGFR activation was indicated to ameliorate gastric tumor development through a delay in growth, induction of apoptosis, as well as inhibition of metastasis and angiogenesis ( 26 ). PAK1 is the best-characterized member of an evolutionarily conserved family of serine/threonine kinases, which has a key role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Detection and analysis of angiogenesis pathway‑associated lncRNA expression profiles in human skin fibroblasts under high‑glucose conditions

Huang

et al. 2020

Mol Med Rep

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Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) have crucial roles in wound healing and that vascular lesions in diabetic wounds are frequently difficult to heal. However, the role of angiogenesis pathway-associated lncRNAs in wound healing in diabetic patients has remained to be fully elucidated. In the present study, human skin fibroblasts were cultured under high-glucose conditions in vitro to mimic a diabetic environment and the angiogenesis pathway-associated lncRNA expression profile in the high- and normal-glucose groups was examined. The microarray data indicated that 14 lncRNAs and 22 mRNAs were differentially expressed. Several candidate lncRNAs and mRNAs were then analyzed by reverse transcription-quantitative PCR and the results were consistent with the microarray data. Furthermore, the University of California Santa Cruz Genome Browser was used to identify mRNAs linked to angiogenesis pathways near the transcriptional region of lncRNAs. The results suggested that lncRNAs RP4-791C19.1 and CTD-2589O24.1 may act on their target genes epidermal growth factor receptor and p21 (RAC1) activated kinase 1, respectively, as enhancers and cis-regulate their expression. Therefore, the present study confirmed that several angiogenesis pathway-associated lncRNAs were differentially expressed under high-glucose conditions, which may have a key role in wound healing in patients with diabetes.

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The constitutively active PKG II mutant effectively inhibits gastric cancer development via a blockade of EGF/EGFR-associated signalling cascades

Cited by 17 publications

References 41 publications

Active PKG II inhibited the growth and migration of ovarian cancer cells through blocking Raf/MEK and PI3K/Akt signaling pathways

Active PKG II inhibited the growth and migration of ovarian cancer cells through blocking Raf/MEK and PI3K/Akt signaling pathways

Construction and comprehensive analysis of dysregulated long non‐coding RNA‐associated competing endogenous RNA network in clear cell renal cell carcinoma

Detection and analysis of angiogenesis pathway‑associated lncRNA expression profiles in human skin fibroblasts under high‑glucose conditions

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