Sweet-P inhibition of glucocorticoid receptor β as a potential cancer therapy.

Cancer cell & microenvironment Pub Date : 2016-01-01 Epub Date: 2016-07-05
Assumpta C Nwaneri, Lucien McBeth, Terry D Hinds
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Abstract

The need for the development of new cancer therapies and push for the design of new targeting techniques is on the rise, and would be useful for cancers that are resistant to current drug treatments. The understanding of the genome has significantly advanced cancer therapy, as well as prevention and earlier detection. This research highlight discusses a potential new type of cancer-targeting molecule, Sweet-P, which is the first of its kind. Sweet-P specifically targets the microRNA-144 binding site in the 3' untranslated region (3' UTR) of the human glucocorticoid receptor β (GRβ), which has been demonstrated to increase expression. GRβ has been shown to be highly expressed in cells from solid tumors of uroepithelial carcinomas, gliomas, osteosarcomas, and hepatocellular carcinomas, as well as in liquid tumor cells from leukemia patients. In non-cancerous diseases, GRβ has been shown to be highly expressed in glucocorticoid-resistant asthma. These maladies brought the need for the development of the Sweet-P anti-GRβ molecule. Sweet-P was shown to repress the migration of bladder cancer cells, and may serve as a new therapeutic for GRβ-related diseases.

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糖皮质激素受体β的Sweet-P抑制作为潜在的癌症治疗方法。
开发新的癌症治疗方法和推动设计新的靶向技术的需求正在上升,这将有助于治疗对当前药物治疗有抗药性的癌症。对基因组的了解大大促进了癌症治疗,以及预防和早期发现。本研究重点讨论了一种潜在的新型癌症靶向分子,Sweet-P,这是同类分子中的第一个。Sweet-P特异性靶向人糖皮质激素受体β (GRβ) 3'非翻译区(3' UTR)的microRNA-144结合位点,已被证明可增加表达。GRβ已被证明在尿上皮癌、胶质瘤、骨肉瘤和肝细胞癌等实体瘤细胞以及白血病患者的液体肿瘤细胞中高度表达。在非癌性疾病中,GRβ已被证明在糖皮质激素抵抗性哮喘中高表达。这些疾病带来了开发Sweet-P抗gr β分子的需求。Sweet-P可抑制膀胱癌细胞的迁移,可能成为治疗gr β相关疾病的新方法。
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