PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Zhang, Haiping; Yu, Ziliang; Wu, Bingbing; Sun, Farui

doi:10.1186/s13018-020-01679-6

Cited by 11 publications

(10 citation statements)

References 26 publications

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“…The PI3K/Akt pathway is well known to be a classic signaling pathway involved in the regulation of various functions, including cell survival, proliferation, invasion, and migration 18 . The experimental results described above showed that cadherin-11 was up-regulated by inflammatory factors.…”

Section: Resultsmentioning

confidence: 99%

“…Although the results confirmed that IL-1β and TNF-α could up-regulate cadherin-11 expression, the specific molecular mechanism remains unclear. The PI3K/Akt pathway has been well-established as a classic signaling pathway involved in the regulation of various functions (cell survival, proliferation, invasion, and migration) 18 . A study conducted by Alkhadar reported that nerve growth factors were triggered by the PI3K/Akt pathway in oral and salivary tumor cells and induced oral and salivary tumor cells scattering and migration 33 .…”

Section: Discussionmentioning

confidence: 99%

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Cadherin-11 cooperates with inflammatory factors to promote the migration and invasion of fibroblast-like synoviocytes in pigmented villonodular synovitis

Cao¹,

Wu²,

Niu³

et al. 2020

Theranostics

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Rationale: Pigmented villonodular synovitis (PVNS) is a destructive benign tumor-like hyperplastic disease that occurs in synovial tissue. Fibroblast-like synoviocytes (FLS) are the predominant cell type comprising the structure of the PVNS synovial lining layer. Due to a high recurrence rate, high invasion, migration, and cartilage destruction ability, PVNS causes substantial damage to patients and the efficacy of surgical resection is not satisfactory. Therefore, exploring the pathogenesis and identifying novel therapeutic targets for PVNS are urgently required. Currently, the pathogenesis of PVNS remains unclear, and there is uncertainty and controversy regarding whether PVNS is an inflammatory or a neoplastic disease. Cadherin-11 is a classical molecule that mediates hemophilic cell-to-cell adhesion in FLS and plays an important role in the normal synovium lining layer formation. This study aimed to explore the role of inflammation and cadherin-11 in PVNS pathogenesis and determine the effects of cadherin-11 as a molecular target for PVNS treatment. Methods: FLS were primarily cultured from PVNS patients during arthroscopic synovectomy. The level of cytokines in the PVNS synovial fluid was evaluated using a human antibody array. Cadherin-11 expression of PVNS FLS was detected by qPCR, Western blots, tissue immunohistochemistry, and cell immunofluorescence. Cadherin-11 was down-regulated by siRNA or up-regulated with a plasmid, with or without inflammatory factor stimulation, and PI3K/Akt was inhibited with LY294002. The capacity of migration and invasion of PVNS FLS was tested using Transwell and wound-healing assays. Activation of the nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was detected by Western blots. Chondrocyte damage by PVNS FLS was assessed with a co-culture assay. Results: Inflammatory factors (IL-1β and TNF-α) in the synovial fluid of PVNS patients were significantly up-regulated. Cadherin-11 was highly expressed in the FLS of PVNS patients, and positively correlated with recurrence, extra-articular migration, and cartilage destruction of PVNS. Knocking down of cadherin-11 inhibited the migration and invasion of PVNS FLS. Moreover, inflammatory factors up-regulated the expression of cadherin-11, which activated the NF-κB and MAPK signaling pathways and led to cartilage destruction. Inhibition of cadherin-11 blocked IL-1β- and TNF-α-induced activation of the above pathways, migration and invasion of PVNS FLS, and damage of chondrocyte. In addition, the elevation of cadherin-11 expression, together with the migration and invasion, of PVNS FLS was down-regulated by the inhibition of the PI3K/Akt signaling pathway. Conclusions: Cadherin-11 plays an important role in the pathogenesis of PVNS and forms a positive feedback loop with inflammatory factors, which further activates the NF-κB and MAPK pathways to trigger an inflammatory cascade. Cadherin-11-mediated inflammation ...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cadherin-11 cooperates with inflammatory factors to promote the migration and invasion of fibroblast-like synoviocytes in pigmented villonodular synovitis

Cao¹,

Wu²,

Niu³

et al. 2020

Theranostics

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“…On the other hand, we identified several hub RNAs based on the PPI network, including HP, CRH, GCG, APOA5, and PENK. Some of these genes are involved in the development of cancer, for instance, PENK is downregulated in osteosarcoma and can activate the PI3K/Akt signaling pathway to restrain osteosarcoma cell migration ( Zhang et al, 2020 ). Notably, PENK was also downregulated in our PPI network.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Survival-Related lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Gastric Cancer

Zhao

Zhang

et al. 2021

Front. Genet.

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To analyze and construct a survival-related endogenous RNA (ceRNA) network in gastric cancer (GC) with lymph node metastasis, we obtained expression profiles of long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs) in GC from The Cancer Genome Atlas database. The edgeR package was used to screen differentially expressed lncRNAs, mRNAs, and miRNAs between GC patients with lymphatic metastasis and those without lymphatic metastasis. Then, we used univariate Cox regression analysis to identify survival-related differentially expressed RNAs. In addition, we used multivariate Cox regression analysis to screen lncRNAs, miRNAs, and mRNAs for use in the prognostic prediction models. The results showed that 2,247 lncRNAs, 155 miRNAs, and 1,253 mRNAs were differentially expressed between the two patient groups. Using univariate Cox regression analysis, we found that 395 lncRNAs, eight miRNAs, and 180 mRNAs were significantly related to the survival time of GC patients. We next created a survival-related network consisting of 59 lncRNAs, seven miRNAs, and 36 mRNAs. In addition, we identified eight RNAs associated with prognosis by multivariate Cox regression analysis, comprising three lncRNAs (AC094104.2, AC010457.1, and AC091832.1), two miRNAs (miR-653-5p and miR-3923), and three mRNAs (C5orf46, EPHA8, and HPR); these were used to construct the prognostic prediction models, and their risk scores could be used to assess GC patients’ prognosis. In conclusion, this study provides new insights into ceRNA networks in GC and the screening of prognostic biomarkers for GC.

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“…PENK is also associated with the progression of head, neck, gastrointestinal stromal tumours and pancreatic cancer. 27 SST is a cyclic peptide hormone, which affects the secretion of growth hormone, gastrointestinal motility and gastrointestinal blood flow. 28 In pancreatic cancer, SST may be a promising therapeutic site, which can get stem cells rest to inhibit colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Immune and stromal related genes in colon cancer: Analysis of tumour microenvironment based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases

Jia

Zhou

et al. 2021

Scand J Immunol

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The incidence of colon cancer is amongst the top three in the world. The tumour microenvironment plays an important role in the occurrence and development of colon cancer. Stromal cells and immune cells are the main components of the tumour microenvironment. Our study detected genes, which affected the infiltration of stromal, immune cells and the way they affected the prognosis of colon cancer patients. We found that the colon's immune system had a special way to affect the tumour microenvironment. Moderate infiltration of stromal and immune cells was proved to be important protective factors for colon cancer patients, which has not been found in other tumours. C3, C5, CXCL12, GNAI1, LPAR1, PENK, PYY, SAA1 and SST were the differential expression hub genes of moderate-stromal and immune score group. They had a more significant correlation with tumour purity and infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophage, neutrophil, democratic cells. The proteins encoded by C3, C5, CXCL12, GNAI1, PENK, PYY, SST were detected in colon cancer cells. These genes had the potential to become markers to predict the prognosis of patients with colon cancer.How to cite this article: Wu Y, Jia H, Zhou H, et al. Immune and stromal related genes in colon cancer: Analysis of tumour microenvironment based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases.

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PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Cited by 11 publications

References 26 publications

Cadherin-11 cooperates with inflammatory factors to promote the migration and invasion of fibroblast-like synoviocytes in pigmented villonodular synovitis

Cadherin-11 cooperates with inflammatory factors to promote the migration and invasion of fibroblast-like synoviocytes in pigmented villonodular synovitis

Comprehensive Analysis of Survival-Related lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Gastric Cancer

Immune and stromal related genes in colon cancer: Analysis of tumour microenvironment based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases

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