ZNF139 promotes tumor metastasis by increasing migration and invasion in human gastric cancer cells

Li, Y; Tan, Bing; Zhao, Qingchun; Fan, Li; Wang, D; Liu, Y

doi:10.4149/neo_2014_037

Cited by 34 publications

(26 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In gastric cell lines, it has also been shown to promote migration, invasion, and multidrug resistance [41,42]. Knockdown of ZKSCAN1 in GC cell lines leads to changes in expression of MMP2 , MMP9 , ICAM1 , and TIMP1 , impacting cell adhesion and matrix metalloprotease activities [42]. BCL-2 and other modulators of apoptosis are also among the ZKSCAN1 targets [41].…”

Section: Discussionmentioning

confidence: 99%

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study

et al. 2016

View full text Add to dashboard Cite

BackgroundLung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression.Methods and FindingsWe performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10−50). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5×10−4) were associated with increased risk of distant metastasis. Our study’s limitations include a small number of LUAD patients for subgroup analyses and a single-sample design for investigation of subclonality.ConclusionsThese data provide a genomic characterization of LUAD pathogenesis and progression. The distinct clonal and subclonal mutation signatures suggest possible diverse carcinogenesis pathways for endogenous and exogenous exposures, and may serve as a foundation for more effective treatments for this lethal disease. LUAD’s high heterogeneity emphasizes the need to further study this tumor type and to associate genomic findings with clinical outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Li et al (66) demonstrated that zinc finger protein 139 (ZNF139) regulated ANXA1 and ANXA5 expression, and promoted the LN metastasis of GC. ZNF139 is associated with multidrug resistance, and may promote GC invasion and metastasis (67,68).…”

Section: Alterations In Gene Expression In Metastatic Lnsmentioning

confidence: 99%

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

Zhu

Hu²,

Wei

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Gastric cancer (GC) is one of the deadliest types of cancer in the world. Lymph node (LN) metastasis is a complex and malignant behavior of GC, involving a sequence of biological processes, including decreased adherence to adjacent cells, extracellular matrix (ECM) degradation and lymphatic channel permeation. LN metastasis is directly associated with the treatment response, local recurrence and long-term survival of patients with GC. Therefore, the molecular mechanisms of LN metastasis in GC development require further investigation. Recently, a large number of clinical studies have focused on the molecular mechanisms and biological markers of tumor invasion and metastasis. However, few articles have broadly summarized LN metastasis in GC, and the molecular mechanisms of LN metastasis are not yet fully understood. In the present review, the molecular mechanisms of LN metastasis in GC will be discussed, including the following aspects: Cell adhesion and movement, ECM degradation, new vessel formation, and molecular pattern differences between metastatic LNs and the primary tumor. This review may lead to a better understanding of LN metastasis in GC, and the identification of new diagnostic markers.

show abstract

“…van Dekken et al [13] discovered that the expression of ZNF139 was increased in adenocarcinoma of esophago–gastric junction. Also, ZNF139 can promote the invasion and progression of GC cells [15]. After using RNAi technique to suppress the expression of ZNF139, we found that gastric cell line MKN28 became more sensitive to chemotherapeutic drugs, and related drug-resistance genes varied [16].…”

Section: Discussionmentioning

confidence: 99%

“…van Dekken et al [13] discovered that the expression of ZNF139 increased in cancer tissues of the gastro–esophageal junction and may be related to cancer growth and development, and the same research team also revealed that ZNF139 has participated in the process of gastric cells differentiation [14], promoting invasion and development of GC cells [15]. Furthermore, the increased expression of ZNF139 is also closely related to GC MDR [16].…”

Section: Introductionmentioning

confidence: 99%

ZNF139 increases multidrug resistance in gastric cancer cells by inhibiting miR-185

et al. 2018

View full text Add to dashboard Cite

It has been reported that the expression of zinc finger protein 139 (ZNF139) and microRNA-185 (miR-185) were associated with proliferation, drug resistance of gastric cancer (GC) cells. However, the detailed mechanisms have not been fully investigated. The expression of ZNF139 in both GC tissues and cell lines was tested, then SGC7901/ADR or SGC7901 cells were transfected with ZNF139-siRNA, miR-185 analog, or pcDNA-ZNF139. Cell activity was determined by MTT assay. Real-time PCR and Western blot were utilized to detect ZNF139, miR-185, and multidrug resistance (MDR) related genes including MDR1/P-gp, GST-π, MRP-1, Bcl-2, TS and Bax. ChIP and dual luciferase activity assay were used to investigate regulation between ZNF139 and miR-185. Increased ZNF139 and decreased miR-185 expression were detected in GC tissues and cell lines. Transfection with ZNF139-siRNA into SGC7901/ADR cells markedly increased expression of miR-185, and treating with chemotherapeutic drugs ADR, 5-FU, L-OHP, the survival rate of SGC7901/ADR cells obviously decreased after ZNF139-siRNA transfection. On the other hand, transfection with pcDNA-ZNF139 in GC cell line SGC7901 resulted in an increased expression level of ZNF139 and a decline in the expression level of miR-185, meanwhile drug resistance of GC cells was clearly enhanced to ADR, 5-FU, L-OHP. Dual luciferase activity assay demonstrated that ZNF139 inhibited transcriptional activities of miR-185’s promoter in cells transfected with the reporter plasmid encompassing the upstream promoter region of miR-185 along with pcDNA-ZNF139. Our data reveal that ZNF139 might promote MDR gene MDR1/P-gp, MRP-1 and Bcl-2 by prohibiting miR-185.

show abstract

ZNF139 promotes tumor metastasis by increasing migration and invasion in human gastric cancer cells

Cited by 34 publications

References 23 publications

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

ZNF139 increases multidrug resistance in gastric cancer cells by inhibiting miR-185

Contact Info

Product

Resources

About