Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma

Lin, Bonan; Zhou, Xiaomeng; Lin, Shuye; Wang, Xiaoyue; Zhang, Meiying; Cao, Bowen; Dong, Yan; Yang, Shuai; Wang, Ji Ming; Guo, Mingzhou; Huang, Jiaqiang

doi:10.1007/s00109-017-1578-5

Cited by 15 publications

(47 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C; Supplementary Table S7). The in vitro methylation DNA (IVD) that served as the positive control was the A & D Human Methylated DNA Standard (A & D Technology), and the negative control was the genomic DNA from normal human peripheral lymphocytes as described (35). MSP products were analyzed using a 2% agarose gel electrophoresis.…”

Section: Rna Isolation Reverse Transcription and Pcrmentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) assay was performed following the EpiTech ChIPOneDay Kit protocol (QIAGEN) as described (15,35). GES-1 cells with shMT2A stable transfection (GES-1-shMT2A), nonspecific control (GES-1-shNC) or BGC823 cells were fixed with 1% formaldehyde.…”

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

“…BGC823 or GES-1 cells were seeded in soft agar in six-well tissue culture plates (0.1-0.2 Â 10 3 cells/well) in triplicate. Colonies with more than 50 cells were counted after 2 weeks by following the previous protocol (15,35).…”

Section: Colony Formationmentioning

confidence: 99%

“…After 18 hours for BGC823, 24 hours for GES-1 cells, the cells that migrated to the lower chamber were fixed and stained with 0.2% crystal violet (Beyotime; ref. 35).…”

Section: Cell Monolayer Scratching Migrationmentioning

confidence: 99%

See 3 more Smart Citations

Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A

Lin

Wang

Pan

et al. 2019

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Metallothionein 2A (MT2A) suppresses the progression of human gastric cancer potentially through an "MT2A-NF-kB pathway" with unclear mechanisms. This study explored the role of a transcription factor, myeloid zinc-finger 1 (MZF1), in MT2A-NF-kB pathway and its clinical significance in gastric cancer. Experimental Design: MZF1 expression and function in gastric cancer were investigated in vitro and in vivo. The relationship between MZF1 and MT2A was determined by gain-offunction and loss-of-function assays in gastric cancer cells and an immortalized gastric cell line GES-1. The prognostic value of MZF1 expression in association with MT2A was evaluated using IHC in two cohorts. Results: MZF1 was epigenetically silenced in human gastric cancer cell lines and primary tumors. Overexpression of MZF1 in gastric cancer cells suppressed cell proliferation and migration, as well as the growth of xenograft tumors in nude mice. Knocking-down of MZF1 transformed GES-1 cells into a malignant phenotype characterized by increased cell growth and migration. Mechanistically, MZF1 was upregulated in both GC and GES-1 cells by MT2A ectopically expressed or induced upon treatment with a garlic-derived compound, diallyl trisulfide (DATS). MZF1 associated with MT2A was colocalized in the nuclei of GES-1 cells to target the promoter of NF-kB inhibitor alpha (NFKBIA). Clinically, MT2A and MZF1 were progressively downregulated in clinical specimens undergoing gastric malignant transformation. Downregulation of MT2A and MZF1 was significantly correlated with poorer patient prognosis. Conclusions: MT2A exerts its anti-gastric cancer effects by complexing with MZF1 to target NFKBIA. MT2A/MZF1 may serve as a valuable prognostic marker and a novel therapeutic target for human gastric cancer.

show abstract

Section: Rna Isolation Reverse Transcription and Pcrmentioning

confidence: 99%

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

Section: Colony Formationmentioning

confidence: 99%

“…After 18 hours for BGC823, 24 hours for GES-1 cells, the cells that migrated to the lower chamber were fixed and stained with 0.2% crystal violet (Beyotime; ref. 35).…”

Section: Cell Monolayer Scratching Migrationmentioning

confidence: 99%

See 2 more Smart Citations

Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A

Lin

Wang

Pan

et al. 2019

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent studies suggest that PRSS3 is aberrantly expression in human cancers and participates in the development and progression of cancer by acting as an oncogene or a tumour suppressor. For example, PRSS3 was identified to be downregulated in non-small cell lung cancer and hepatocellular carcinoma [6,7]. On the contrary, high PRSS3 was found in epithelial ovarian cancer and breast cancer [8,9], implying that PRSS3 functions in a cell-or disease-context-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression

Xing

Wang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Pancreatic cancer (PC) is a highly lethal human cancer. We previously found that Serine protease 3 (PRSS3), as an oncogene, is significantly upregulated in PC. In this study, we aimed to investigate the potential mechanism of PRSS3 dysregulation in PC. In this research, low miR-217 and high circ-ADAM9 expression were found in PC tissues and cell lines, which was closely associated with advanced clinical stage and lymph node metastasis. Patients with low miR-217 or high circ-ADAM9 expression had shorter survival time than those with high miR-217 or low circ-ADAM9 expression. Functionally, manipulation of miR-217 and circ-ADAM9 expression showed opposite effects on cell proliferation, migration and invasion. Stepwise mechanism studies indicated that circ-ADAM9 alleviated the inhibitory effect of miR-217 on PRSS3 by directly sponging miR-217 to increase the expression level of PRSS3, resulting in the activation of ERK/VEGF signalling pathway. In vivo, circ-ADAM9 silencing or miR-217 overexpression evidently retarded the growth of tumour, and the combination of them exhibited an additive inhibitory effect on tumourigenicity. Briefly, the ceRNA regulatory network of circ-ADAM9/ miR-217/PRSS3 plays a pivotal role in PC progression by the regulation of ERK/VEGF signalling pathway.

show abstract

Shear Stress Drives the Cleavage Activation of Protease‐Activated Receptor 2 by PRSS3/Mesotrypsin to Promote Invasion and Metastasis of Circulating Lung Cancer Cells

Zhou

Luo

2023

Advanced Science

View full text Add to dashboard Cite

When circulating tumor cells (CTCs) travel in circulation, they can be killed by detachment‐induced anoikis and fluidic shear stress (SS)‐mediated apoptosis. Circulatory treatment, which can make CTCs detached but also generate SS, can increase metastasis of cancer cells. To identify SS‐specific mechanosensors without detachment impacts, a microfluidic circulatory system is used to generate arteriosus SS and compare transcriptome profiles of circulating lung cancer cells with suspended cells. Half of the cancer cells can survive SS damage and show higher invasion ability. Mesotrypsin (PRSS3), protease‐activated receptor 2 (PAR2), and the subunit of activating protein 1, Fos‐related antigen 1 (FOSL1), are upregulated by SS, and their high expression is responsible for promoting invasion and metastasis. SS triggers PRSS3 to cleave the N‐terminal inhibitory domain of PAR2 within 2 h. As a G protein‐coupled receptor, PAR2 further activates the Gαi protein to turn on the Src‐ERK/p38/JNK‐FRA1/cJUN axis to promote the expression of epithelial–mesenchymal transition markers, and also PRSS3, which facilitates metastasis. Enriched PRSS3, PAR2, and FOSL1 in human tumor samples and their correlations with worse outcomes reveal their clinical significance. PAR2 may serve as an SS‐specific mechanosensor cleavable by PRSS3 in circulation, which provides new insights for targeting metastasis‐initiating CTCs.

show abstract

Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma

Abstract: • PRSS3 is downregulated by intragenic hypermethylation in HCC. • Epigenetic silencing of PRSS3 facilitates growth, migration, and invasion of HCC. • PRSS3 intragenic methylation has implication in diagnosis of HCC.

Cited by 15 publications

References 49 publications

Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A

Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A

Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression

Shear Stress Drives the Cleavage Activation of Protease‐Activated Receptor 2 by PRSS3/Mesotrypsin to Promote Invasion and Metastasis of Circulating Lung Cancer Cells

Contact Info

Product

Resources

About