Abstract
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.
Highlights
Gastric cancer (GC) is one of the most common malignancies in digestive tract worldwide with highest incidence and mortality rates [1,2]
Expression of zinc finger protein 139 (ZNF139) was detected via qRT-PCR and Western blot in both GC and gastric para-carcinoma tissues, and the cellular sensitivity of L-OHP was determined by MTT
ZNF139 was up-regulated in GC tissues (Figure 1A,B, qRT-PCR as well as Western blot), compared with that in gastric para-carcinoma tissue (P
Summary
Gastric cancer (GC) is one of the most common malignancies in digestive tract worldwide with highest incidence and mortality rates [1,2]. Surgical removal of lesions is still the main treatment for GC; given that most patients are diagnosed at advanced stage, the outcome of surgical approach is limited [5,6]. Chemotherapy plays a key role in eradicating malignant cells [7,8], the outcome is still not satisfactory with a 5-year survival rate less than 30% [9]. This is mainly attributed to multidrug resistance (MDR) in GC cells. MDR in GC is the main reason for chemotherapy failure, which leads to high mortality rate in GC patients [10,11,12].
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