MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

Zhang, Xiangliang; Shi, Huijuan; Wang, Jiping; Tang, Hua; Wu, Yinbing; Fang, Zhiyuan; Cui, Shuzhong; Wang, Liantang

doi:10.3748/wjg.v20.i32.11347

Cited by 43 publications

(25 citation statements)

References 39 publications

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“…In addition, miR-218 has been found to modulate chemosensitivity in human gastric cancer cells [39], and restoration of miR-218 expression increases cisplatin sensitivity, and induces apoptosis, in cisplatinresistant MCF-7 cells by targeting BRCA1 [17]. We find that experimental overexpression of miR-218 in both MCF-7/A02 and CALDOX cells restores short-term sensitivity and long-term proliferation in the presence of doxorubicin and taxol.…”

Section: Discussionmentioning

confidence: 63%

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Yagüe

2015

Breast Cancer Res Treat

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Multidrug resistance (MDR) remains one of the most significant obstacles in breast cancer treatment, and this process often involves dysregulation of a great number of microRNAs (miRNAs). Some miRNAs are indicators of drug resistance and confer resistance to chemotherapeutic drugs, although our understanding of this complex process is still incomplete. We have used a combination of miRNA profiling and real-time PCR in two drug-resistant derivatives of MCF-7 and Cal51 cells. Experimental modulation of miR expression has been obtained by retroviral transfection. Taxol and doxorubicin IC50 values were obtained by short-term drug sensitivity assays. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays and the levels of apoptosis-related proteins bcl-2 and bax by real-time PCR and Western blot. miR target was studied using transient transfection of luciferase constructs with the 3 untranslated regions (UTR) of target mRNAs. Small interfering RNA-mediated genetic knock-down was performed in MDR cells and its modulatory effect on apoptosis examined. The effect of miRNA on tumorigenicity and tumor drug response was studied in mouse xenografts. miRNA profiling of two drug-resistant breast cancer cell models indicated that miR-218 was down-regulated in both MCF-7/A02 and CALDOX cells. Ectopic expression of miR-218 resensitized both drug-resistant cell lines to doxorubicin and taxol due to an increase in apoptosis. miR-218 binds survivin (BIRC5) mRNA 3-UTR and down-regulated reporter luciferase activity. Experimental down-regulation of survivin by RNA interference in drug-resistant cells did mimic the sensitization observed when miRNA-218 was up-regulated. In addition, resensitization to taxol was also observed in mouse tumor xenografts from cells over-expressing miR-218. miR-218 is involved in the development of MDR in breast cancer cells via targeting survivin and leading to evasion of apoptosis. Targeting miR-218 and survivin may thus provide a potential strategy for reversing drug resistance in breast cancer

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Section: Discussionmentioning

confidence: 63%

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Yagüe

2015

Breast Cancer Res Treat

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“…For instance, Tie et al (2010) found that miR-218 inhibits invasion and metastasis in gastric cancer by targeting the ROBO1 receptor. Zhang et al (2014) reported that this miRNA is upregulated following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer, and increases chemosensitivity to cisplatin, indicating that targeting miR-218 might provide a strategy to block the development of this illness and reverse multidrug resistance of gastric cancer cells. Their subsequent research efforts found that miR-218 levels are lower in multidrug-resistant gastric cancer cells than in chemosensitive parental cells.…”

Section: Discussionmentioning

confidence: 99%

miR-218 tissue expression level is associated with aggressive progression of gastric cancer

Wang¹,

Ge²,

Wang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of the present study was to investigate the clinical significance of microRNA-218 (miR-218) in gastric cancer. We enrolled 112 patients having undergone surgery for gastric cancer between May 2008 and June 2014. Expression of miR-218 was determined by real-time quantitative reverse transcription-polymerase chain reaction. Survival curves were plotted using the Kaplan-Meier method and compared by the log-rank test. We found that miR-218 expression was significantly downregulated in gastric cancer tissues compared to adjacent normal tissues (P < 0.001). Low miR-218 expression was significantly associated with tumor differentiation (P < 0.001), depth of tumor invasion (P = 0.006), and tumor node metastasis stage (P < 0.001). Kaplan-Meier survival analysis revealed that patients with low miR-218 levels showed significantly lower 5-year overall survival than those demonstrating high expression (P = 0.04). Multivariate Cox regression analyses indicated that low miR-218 expression constitutes an independent molecular biomarker for prediction of poor overall survival of gastric cancer patients (hazard ratio = 3.187, 95% confidence interval = 1.551-8.365, P = 0.037). In conclusion, miR-218 was remarkably downregulated in gastric cancer tissues and may serve as a prognostic biomarker for patients suffering from this disease.

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“…Their work used miRNA microarrays to identify an 8-fold increase in miR-218 expression after CRS-HIPEC. 71 Notably, miR-218 increased the sensitivity of the gastric cancer cells to in vitro cisplatin. miR-218.…”

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confidence: 99%

“…75 While no prospective trials have been carried out, studies have indicated that measurement of serum levels of these markers in combination, can be used for preoperative staging and monitoring the effects of therapy postoperatively and after chemotherapy. 71 Additionally, Wang et al, 76 reported that an evaluation of CEA tissue staining showed good correlations with serum CEA and prognosis. Jung et al measured CEA in both serum and ascites from 119 patients with peritoneal metastasis.…”

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confidence: 99%

Current perspectives on hyperthermic intraperitoneal chemotherapy in gastric cancer

Smith¹,

Kirkpatrick²,

Thomas³

et al. 2017

GICTT

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Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective treatment in a variety of cancers with peritoneal carcinomatosis (PC), especially in pseudomyxoma peritonei for which it is the standard of care. The data for gastric cancer are not as conclusive. This review discusses the effect of HIPEC on gastric cancer survival, the importance of patient selection, the effect of HIPEC on gastric cancer morbidity, translational research on HIPEC, and other recent research on HIPEC in the setting of gastric cancer and/or peritoneal metastases. CRS-HIPEC has been shown to be superior to either CRS alone or systemic chemotherapy alone in terms of improving survival. CRS-HIPEC seems to be the best current treatment for patients with gastric cancer and peritoneal metastases. The international community has recommended it as the treatment for this disease. Prudent patient selection before CRS-HIPEC is recommended as subgroups of patients have been shown to benefit from the treatment, while others have not. Studies on CRS-HIPEC have shown the procedure to have acceptably low rates of morbidity and peri-and postoperative complications as well as significant reductions in the incidence of ascites associated with PC. Translational research on HIPEC supports its use as prophylaxis for prevention of peritoneal metastasis and demonstrates HIPEC to be both effective and safe. Measurement of the tumor marker carcinoembryonic antigen has been shown to be an effective indicator of future outcomes in gastric cancer treated with CRS-HIPEC. Although the treatment outcomes have improved, even current treatment using CRS-HIPEC for gastric cancer with PC the survival rates can be dismal. Thus, the treatment of advanced gastric cancer with PC is an ongoing field of study and future directions of the treatment of gastric cancer with PC may include the use of intraperitoneal immunotherapy.

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MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

Abstract: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.

Cited by 43 publications

References 39 publications

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

miR-218 tissue expression level is associated with aggressive progression of gastric cancer

Current perspectives on hyperthermic intraperitoneal chemotherapy in gastric cancer

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