miR-200b and miR-200c as Prognostic Factors and Mediators of Gastric Cancer Cell Progression

Tang, Hailin; Deng, Min; Tang, Yaning; Guo, Jiaoli; Kong, Yanan; Ye, Feng; Qi, Shijie

doi:10.1158/1078-0432.ccr-13-1326

Cited by 150 publications

(131 citation statements)

References 37 publications

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“…We have also observed an inverse correlation between the expression levels of miR200c and that of JNK2, ABCB1, and MMP-2/-9, which predicts the treatment outcome in patients with locally advanced colorectal cancer administrated with standard postsurgery chemotherapy regime (FOLFOX or CapeOX). We further demonstrated that the decreased levels of miR200c correlated with the clinical data of patients responding poorly to chemotherapy (42). It indicates that decreased miR200c expression may be the main mechanism that positively regulates P-gp and MMP-2/-9 expression in MDR colorectal cancer.…”

Section: Discussionmentioning

confidence: 59%

miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer

Sui

Cai

Shu

et al. 2014

Molecular Cancer Therapeutics

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MicroRNA-200c (miR200c) recently emerged as an important regulator of tumorigenicity and cancer metastasis; however, its role in regulating multidrug resistance (MDR) remains unknown. In the current study, we found that the expression levels of miR200c in recurrent and metastatic colorectal cancers were significantly lower, whereas the JNK2 expression was higher compared with primary tumors. We showed that in MDR colorectal cancer cells, miR200c targeted the 3 0 untranslated region of the JNK2 gene. Overexpression of miR200c attenuated the levels of p-JNK, p-c-Jun, P-gp, and MMP-2/-9, the downstream factors of the JNK signaling pathway, resulting in increased sensitivity to chemotherapeutic drugs, which was accompanied by heightened apoptosis and decreased cell invasion and migration. Moreover, in an orthotopic MDR colorectal cancer mouse model, we demonstrated that overexpression of miR200c effectively inhibited the tumor growth and metastasis. At last, in the tumor samples from patients with locally advanced colorectal cancer with routine postsurgical chemotherapy, we observed an inverse correlation between the levels of mRNA expression of miR200c and JNK2, ABCB1, and MMP-9, thus predicting patient therapeutic outcomes. In summary, we found that miR200c negatively regulated the expression of JNK2 gene and increased the sensitivity of MDR colorectal cancer cells to chemotherapeutic drugs, via inhibiting the JNK2/p-JNK/p-c-Jun/ ABCB1 signaling. Restoration of miR200c expression in MDR colorectal cancer may serve as a promising therapeutic approach in MDR-induced metastasis.

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Section: Discussionmentioning

confidence: 59%

miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer

Sui

Cai

Shu

et al. 2014

Molecular Cancer Therapeutics

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“…miRNAs play a vital role in many crucial cellular processes, including apoptosis, differentiation, invasion, and proliferation (32)(33)(34). The abnormal expression of miRNA has been reported in many cancers, including breast (35), gastric (36), colorectal (37), and liver cancers (38), as well as leukemia (39) and lymphoma (40). miR-124 has been described as a brain-specific miRNA in mammals, and may play a role in defining and maintaining neuron-specific characteristics (41,42).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Sun

et al. 2016

Oncology Reports

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Abstract. MicroRNA (miRNA) is a type of endogenous non-coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines. To study the functional significance of miR-124, we overexpressed miR-124 with miR-124 mimics and observed breast cancer cell proliferation, colony formation, migration, and invasion abilities by in vitro cell culture experiments. Target prediction algorithms and luciferase reporter gene assays were used to identify the target genes of miR-124. We also knocked down miR-124 targets using short hairpin RNA (shRNA) constructs, and observed associated breast cancer cell characteristics by in vitro cell culture experiments. We found that miR-124 expression significantly decreased in breast cancer tissues and cells compared to normal tissues and cells. In addition, cell proliferation, colony formation, migration, and invasion were decreased after overexpression of miR-124 in breast cancer cells. Furthermore, we used several algorithms to identify the snail family zinc finger 2 (SNAI2) as a potential target gene of miR-124. The protein expression level and luciferase activity of the 3'-untranslated region of SNAI2 were significantly decreased in breast cancer cells transfected with miR-124 mimics. Cell proliferation, colony formation, migration, and invasion were also decreased after knockdown of SNAI2 by shRNA. In conclusion, our data suggest that miR-124 expression is decreased in breast cancer and plays an important role as a tumor suppressor gene by targeting SNAI2. These findings may reveal novel perspectives for clinical treatments against breast cancer.

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“…miR-200c is a member of the miR-200 family, which was previously shown to inhibit epithelialto-mesenchymal transition (EMT) by targeting the transcriptional repressor of cadherin 1(CDH1), zinc finger E-box binding homeobox 1 (ZEB1), and survival of motor neuron protein interacting protein 1(SIP1); this suggests that these miRNAs could prevent tumor progression by negatively regulating ZEB transcriptional repressors and consequently maintaining E-cadherin junctions and preventing EMT (Bracken et al, 2008;Gregory et al, 2008;Korpal et al, 2008;Park et al, 2008). Upregulation of miR-200c had been found in several cancers, including ovarian cancer (Iorio et al, 2007;Bendoraite et al, 2010), cervical cancer , bile duct cancer (Meng et al, 2006), nasopharyngeal carcinoma (Zhang et al, 2010), lung cancer (Liu et al, 2012), and colorectal cancer (Zhang et al, 2013;Cristobal et al, 2014), as well as GC (Tang et al, 2013;Song et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Related studies have shown that human serum contains miRNAs and that their expression patterns can potentially be used as clinically diagnostic and prognostic biomarkers of various cancers (Cortez et al, 2009(Cortez et al, , 2012. ) is a member of the miR-200 family, which is overexpressed in several cancers, including ovarian cancer (Iorio et al, 2007;Bendoraite et al, 2010), cervical cancer , bile duct cancer (Meng et al, 2006), nasopharyngeal carcinoma (Zhang et al, 2010), lung cancer (Liu et al, 2012), colorectal cancer (Zhang et al, 2013;Cristobal et al, 2014), and GC as well (Tang et al, 2013;Song et al, 2014). Valladares-Ayerbes et al (2012) found that the miR-200c blood expression levels in GC patients were significantly higher than in normal controls (P = 0.018) and that it has the potential to be a predictor of progression and survival.…”

Section: Introductionmentioning

confidence: 99%

Serum miR-200c expression level as a prognostic biomarker for gastric cancer

Hp¹,

Fb²,

Sj³

2015

Genet. Mol. Res.

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ABSTRACT. The aim of the present study was to analyze the serum expression level of in gastric cancer (GC) patients and to determine the relationship between this expression and clinicopathological features and survival. Serum samples were obtained from 98 patients with GC between February 2008 and January 2013. Quantitative RT-PCR was used to assess miR-200c expression levels in serum samples. Survival curves were plotted using the Kaplan-Meier method, and differences between survival curves were compared by the log rank test. The Cox proportional hazard regression model was used to analyze the risk factors for GC. Relative serum miR-200c level was found to be significantly higher in patients with GC than healthy controls. Mean serum miR-200c level was 97.43 ± 26.16 in the GC group and 20.79 ± 14.61 in the control group (P < 0.0001). Serum miR-200c level was also significantly associated with tumor grade (P = 0.01) and TNM stage (P = 0.009). Kaplan-Meier survival curves demonstrated that the overall survival rate was significantly lower in the patients with high serum miR-200c level than in those with low levels (27.9 vs 55.9%, P = 0.007). In addition, 15913-15920 (2015) multivariate analysis confirmed that the hazard risk (HR) of death was significantly higher in patients with high serum miR-200c expression levels compared with low expression levels (HR = 4.01, 95%CI = 2.67-10.02, P = 0.006). The relative expression of serum miR-200c in GC patients was significantly higher compared to healthy controls, and it may prove to be useful in assessing the prognosis of GC.

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miR-200b and miR-200c as Prognostic Factors and Mediators of Gastric Cancer Cell Progression

Abstract: Purpose: The purpose of this study was to investigate the clinicopathologic significance and potential role of miR-200b and miR-200c

Cited by 150 publications

References 37 publications

miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer

miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Serum miR-200c expression level as a prognostic biomarker for gastric cancer

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