Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9

Yang, Feilong; Yu, Nengwang; Wang, Hui; Zhang, Cong; Zhao, Zhongwei; Li, Yanxiang; Yan, Lei; Liu, Hainan; Xu, Zhonghua

doi:10.1371/journal.pone.0190725

Cited by 31 publications

(21 citation statements)

References 31 publications

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“…MMPs are proteolytic enzymes that participate in the degradation of extracellular matrix, which can promote cancer progression by increasing its growth, migration, invasion, metastasis and angiogenesis (29,30). Downregulation of MMP2 and MMP9 inhibits tumor cell migration and invasion (31,32). STAT proteins, particularly STAT3, are activated in a large number of human cancer types (33).…”

Section: Discussionmentioning

confidence: 99%

miR‑613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD

Gao

Feng

et al. 2020

Exp Ther Med

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Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and has a high mortality rate. MicroRNAs (miRs) are a family of post-transcriptional regulators, which negatively regulate target gene expression. miR-613 has been revealed to be a diagnostic and prognostic biomarker in ESCC. However, the role of miR-613 in ESCC remains unclear. In the present study, miR-613 expression was identified to be reduced in tumor tissues in comparison with corresponding adjacent normal tissues. TargetScan and a dual-luciferase reporter assay verified glucose-6-phosphate dehydrogenase (G6PD) as a direct target of miR-613. In contrast with miR-613, G6PD expression was increased in tumor tissues compared with matched healthy tissues. Furthermore, overexpression of miR-613 inhibited cell migration and invasion of Eca109 cells compared with controls, while G6PD overexpression reversed the inhibition induced by miR-613, as determined by wound healing and Transwell assays. In addition, miR-613 overexpression decreased the mRNA and protein expression of G6PD, matrix metalloproteinase (MMP)2 and MMP9, and reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) compared with controls, while G6PD reversed the effects of miR-613. However, miR-613 and G6PD did not affect the expression of STAT3. In conclusion, the aforementioned results suggest that miR-613 targets G6PD to suppress ESCC cell migration and invasion through reduced MMP2 and MMP9 expression and inactivation of the STAT3 signaling pathway. Thus, the present study may provide a new molecular foundation for treatment of ESCC.

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Section: Discussionmentioning

confidence: 99%

miR‑613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD

Gao

Feng

et al. 2020

Exp Ther Med

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“…37 MMP-2 and MMP-9 are members of the MMP enzyme family believed to play important role in EMT and cancer metastasis. 38 Previous studies have demonstrated that B7-H3 enhances inflammatory responses and promotes MMP-9 expression in a pneumococcal meningitis animal model. 39 In osteosarcoma, B7-H3 also regulates cell migration and promotes tumor invasion through an MMP-2-associated signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway</p>

Zhong¹,

Tao²,

Chen³

et al. 2020

OTT

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The aim of this study was to explore the potential role of B7-H3 in malignant glioma progression and identify an innovative approach in clinical glioma therapy. Methods: The protein expression of B7-H3 in high-and low-grade tumor tissues from glioma patients was assessed by immunohistochemistry. The proliferative and invasive ability of B7-H3-overexpressing or knockout glioma cells was analyzed in vitro and in vivo by CCK-8 assay and an orthotopic mouse glioma model, respectively. Activation of the JAK2/STAT3/Slug signaling pathway and epithelial-mesenchymal transition (EMT) was examined by Western blotting and immunofluorescence. The anticancer effects of napabucasin (NAP) and temozolomide (TMZ) were analyzed in an orthotopic mouse glioma model. Results: The expression of B7-H3 was higher in high-grade than in low-grade tumor tissues from glioma patients. In line with this, overexpression of B7-H3 enhanced glioma cell proliferation, induced sustained glioma growth, and promoted glioma cell invasion in vitro and in vivo. Moreover, these effects were mediated through the activation of the JAK2/ STAT3/Slug signaling pathway in B7-H3 overexpression glioma cells. We also found that B7-H3 induced EMT processes through downregulation of E-cadherin and upregulation of MMP-2/-9 expression, resulting in enhanced invasion of glioma cells. Finally, we show that the combination of NAP and TMZ significantly suppressed glioma growth and glioma cell invasion, both in vitro and in vivo. Conclusion: B7-H3 overexpression facilitated sustained glioma growth and promoted glioma cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway. Application of the STAT3 inhibitor NAP significantly suppressed glioma growth and invasion, and has potential as a therapeutic strategy for the treatment of glioma.

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“…It has been reported that inhibiting the expression of Ets1 gene could reduce proteins of the MMP9 secretion and significantly inhibit the invasion of PC3 cells ( Kato et al, 2012 ). Yang et al (2018) also indicated that the migration, invasion ability of PCa cells could be inhibited by downregulated the expression of MMP9. As expected, Silybin presented inhibition of ALDH1A1 expression and along with the lower expressions of RARα, Ets1 and MMP9.…”

Section: Discussionmentioning

confidence: 89%

Silybin Prevents Prostate Cancer by Inhibited the ALDH1A1 Expression in the Retinol Metabolism Pathway

Jiang

Song

Jiang

et al. 2020

Front. Cell Dev. Biol.

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Background Silybin was known to exert inhibition in prostate cancer, but the underlying mechanism remained largely unknown. This study was designed to find out the potential target of Silybin on prostate cancer and explore the relative mechanisms. Methods Firstly, we screened the possible targets of Silybin through the PubChem database and Subpathway – GM. Then DU145 cells were transferred to investigate the correction about related targets, magnetic bead sorting and flow cytometry were used to sort and identify the cells. Proliferation, migration and invasion ability of DU145 cells were detected by MTT assay, Transwell assay, plate clonality and sphere formation assay. BALB/c nude mice were constructed models with implanted sarcoma and measured the tumor volume every 5 days as wells tumor weight. The levels of proteins were detected by Western blot and immunocytochemistry. RT-PCR was selected to test the expression of protein’s mRNA. Results It was screened out the ALDH1A1 was highly correlated with subpathways of the Silybin risk metabolic pathway. And ALDH1A1 expression was positively correlated RARα with Ets1 by interfering with the ALDH1A1 gene. Importantly, ALDH1A1(+) cells showed proliferation, migration and invasion ability. In addition, it showed that Silybin exerted the inhibition on prostate cells by suppressed the proliferation, migration and invasion ability of cells in vitro experiment. Silybin also reduced the tumor volume and weight. And Silybin displayed obviously reduced the proteins and mRNA of ALDH1A1, RARα, Ets1 and MMP9 expressions. Conclusion Our results indicated that Silybin showed inhibition of prostate cancer and the mechanism was involving with downregulating ALDH1A1 expression, thereby inhibiting the activation of RARα and preventing the activation of Ets1 to inhibit the growth and invasion of prostate cancer.

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Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9

Cited by 31 publications

References 31 publications

miR‑613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD

miR‑613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD

<p>B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway</p>

Silybin Prevents Prostate Cancer by Inhibited the ALDH1A1 Expression in the Retinol Metabolism Pathway

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