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MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma

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Abstract

Abnormal angiogenesis is critically involved in tumor progression and metastasis including endometrial cancer and is regulated by microRNAs such as microRNA-101 (miR-101). We hypothesize that miR-101 expression is disrupted in endometrial cancer and modulation of miR-101 levels is sufficient to regulate tumor growth through angiogenesis. We examined the expression levels of miR-101 and factors involved in angiogenesis in the patients with endometrial cancer. We also overexpressed or inhibited miR-101 in RL-95-2 cells and examined their effects on cell toxicity and tumor growth. Finally, we determined if miR-101 regulated tumorigenesis through cyclooxygenase-2 (COX-2). We found that miR-101 levels were significantly reduced. Factors involved in angiogenesis included vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and aromatase (P450arom), which were increased in endometrial carcinoma. Modulation of miR-101 level was sufficient to affect tumor growth. Finally, we found that the effects of miR-101 inhibition on tumor growth were suppressed by COX-2 inhibition. Our results suggest that modulating miR-101 and COX-2 levels or their activity may be a potential therapeutic strategy for endometrial cancer.

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  1. The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China

    Ying Liu, Haiyan Li, Congying Zhao & Hanbing Jia

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Correspondence to Haiyan Li.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Liu, Y., Li, H., Zhao, C. et al. MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma. Mol Cell Biochem 448, 61–69 (2018). https://doi.org/10.1007/s11010-018-3313-0

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