MiR-203 promotes the growth and migration of ovarian cancer cells by enhancing glycolytic pathway

Zhao, Xielan; Lichun, Fan; Xie, Ning; Zou, Kejian; Xiao, Xiaolan; Wang, Shaosheng

doi:10.1007/s13277-016-5415-1

Cited by 46 publications

(28 citation statements)

References 26 publications

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“…Zhao et al . have discovered that overexpressing PDH protein could abolish the oncogenic effects of miR-203, including promoting the metastasis of ovarian cancer cells in vivo and shortening the survival of the tumor-bearing nude mice [58]. Taken together, these studies suggest that a high PDH level correlates with a favorable prognosis and a prolonged survival of ovarian cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells

Zhang

et al. 2017

PLoS ONE

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Pyruvate dehydrogenase kinase 1 (PDK1) is overexpressed in ovarian cancer and thus is a promising anticancer therapeutic target. Our previous work suggests that coumarin compounds are potential inhibitors of PDKs. In this study, we used the ovarian cancer cell line SKOV3 as the model system and examined whether dicumarol (DIC), a coumarin compound, could inhibit ovarian cancer through targeting PDK1. We showed that DIC potently inhibited the kinase activity of PDK1, shifted the glucose metabolism from aerobic glycolysis to oxidative phosphorylation, generated a higher level of reactive oxygen species (ROS), attenuated the mitochondrial membrane potential (MMP), induced apoptosis, and reduced cell viability in vitro. The same phenotypes induced by DIC also were translated in vivo, leading to significant suppression of xenograft growth. This study not only identifies a novel inhibitor for PDK1, but it also reveals novel anticancer mechanisms of DIC and provides a promising anticancer therapy that targets the Warburg effect.

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Section: Discussionmentioning

confidence: 99%

Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells

Zhang

et al. 2017

PLoS ONE

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“…In the literature, there are contradicting results concerning miR-203 with some studies supporting a tumor promoting and others a tumor suppressive role. 37,38 However, it has also been suggested that miR-203 has a suppressing role on epithelialmesenchymal transition, by interfering with the TGFb-SMAD3 pathway. 39 In our study, miR-203 expression showed no consistent correlation with ZEB1 or ZEB2 expression, suggesting that it may affect epithelial-mesenchymal transition independently of ZEB1/ZEB2.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer

et al. 2017

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Cellular interactions in the tumor microenvironment influence neoplastic progression in pancreatic ductal adenocarcinoma. One underlying mechanism is the induction of the prognostically unfavorable epithelial-mesenchymal-transition-like tumor budding. Our aim is to explore the expression of microRNAs implicated in the regulation of tumor budding focusing on the microenvironment of the invasive front. To this end, RNA from laser-capture-microdissected material of the main tumor, tumor buds, juxta-tumoral stroma, tumor-remote stroma, and non-neoplastic pancreatic parenchyma from pancreatic cancer cases with (n=7) and without (n=6) tumor budding was analyzed by qRT-PCR for the expression of a panel of miRNAs that are known to be implicated in the regulation of epithelial-mesenchymal transition, including miR-21, miR-183, miR-200b, miR-200c, miR-203, miR-205, miR-210, and miR-217. Here we show that at the invasive front of pancreatic ductal adenocarcinoma, specific microRNAs, are differentially expressed between tumor buds and main tumor cells and between cases with and without tumor budding, indicating their involvement in the regulation of the budding phenotype. Notably, miR-200b and miR-200c were significantly downregulated in the tumor buds. Consistent with this finding, they negatively correlated with the expression of epithelial-mesenchymal-transition-associated E-cadherin repressors ZEB1 and ZEB2 in the budding cells (P<0.001). Interestingly, many microRNAs were also dysregulated in juxta-tumoral compared to tumor-remote stroma suggesting that juxta-tumoral stroma contributes to microRNA dysregulation. Notably, miR-200b and miR-200c were strongly downregulated while miR-210 and miR-21 were upregulated in the juxta-tumoral vs tumor-remote stroma in carcinomas with tumor budding. In conclusion, microRNA targeting in both tumor and stromal cells could represent a treatment option for aggressive pancreatic cancer.

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“…miRNAs play important roles in cancer by acting as tumor suppressors or oncogenes (25)(26)(27). Many aberrantly expressed miRNAs have been reported in EOC and involved in EOC cell proliferation, invasion, migration, metastasis and apoptosis (13,28,29). Therefore, miRNAs may be investigated as diagnostic and prognostic molecular biomarkers and therapeutic targets for patients with EOC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-455 inhibits cell proliferation and invasion of epithelial ovarian cancer by directly targeting Notch1

et al. 2017

Molecular Medicine Reports

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Ovarian cancer (OC) is the fifth leading cause of cancer‑associated mortality among women in developed countries. Numerous microRNAs are aberrantly expressed in epithelial (E) OC, and are involved in EOC formation and progression. As such, microRNAs may be investigated as diagnostic and prognostic molecular biomarkers, and therapeutic targets for patients with EOC. For instance, microRNA‑455 (miR‑455) is abnormally expressed in various types of human cancer. However, details on the expression level, biological roles and underlying mechanism of miR‑455 in EOC remain unclear. In the present study, the expression of miR‑455 in EOC was detected, and its association with clinical characteristics was analysed. The functional roles and underlying mechanisms of miR‑455 in EOC were also investigated. The results revealed that miR‑455 expression in EOC tissues and cell lines was significantly downregulated. Furthermore, miR‑455 downregulation was correlated with tumor size, International Federation of Gynecology and Obstetrics stage and lymph node metastasis of patients with EOC. Restoration of miR‑455 expression efficiently inhibited cell proliferation and invasion in vitro. Notch1 was identified as a direct target of miR‑455 in EOC. The mRNA and protein expression levels of Notch1 were higher in EOC tissues compared with in normal ovarian epithelial tissues. Spearman's correlation analysis indicated that miR‑455 expression was negatively correlated with the mRNA level of Notch1 in EOC tissues. Notch1 overexpression was able to restore the EOC cell proliferation and invasion abilities suppressed by miR‑455. The present study provided evidence that the dysregulation of the miR‑455/Notch1 signalling pathway may be essential for EOC occurrence and development. In addition, the results confirmed the tumor‑suppressive roles of miR‑455 in modulating EOC proliferation and invasion through regulation of Notch1 expression. Thus, miR‑455 may be a novel miRNA‑based therapeutic target to treat patients with EOC.

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MiR-203 promotes the growth and migration of ovarian cancer cells by enhancing glycolytic pathway

Cited by 46 publications

References 26 publications

Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells

Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells

MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer

MicroRNA-455 inhibits cell proliferation and invasion of epithelial ovarian cancer by directly targeting Notch1

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