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mTORC1抑制剂PRP-1对人软骨肉瘤中癌基因和肿瘤抑制性微小RNA的调控

Regulation of onco and tumor suppressor MiRNAs by mTORC1 inhibitor PRP-1 in human chondrosarcoma.

作者信息

Galoian Karina A, Guettouche Toumy, Issac Biju, Qureshi Amir, Temple H T

机构信息

Department of Orthopaedics, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue, Suite 8012 (D27), Miami, FL, 33136, USA,

出版信息

Tumour Biol. 2014 Mar;35(3):2335-41. doi: 10.1007/s13277-013-1309-7. Epub 2013 Nov 1.

Abstract

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. This study aimed to reveal the comparative analysis of miRNAs and their targets in human JJ012 chondrosarcoma cell line between control and experimental samples, treated with mTORC1 inhibitor, cytostatic antiproliferative proline-rich polypeptide (PRP-1). Examination of tumor-specific microRNA expression profiles has revealed widespread deregulation of these molecules in diverse cancers. It was reported that microRNAs can function as novel biomarkers for disease diagnostics and therapy, as well as a novel class of oncogenes and tumor suppressor genes. mTORC 1 inhibitor PRP-1 caused significant upregulation of tumor suppressors, such as miR20a, miR125b, and miR192; and downregulation of onco miRNAs, miR509-3p, miR589, miR490-3p, miR 550 in human chondrosarcoma JJ012 cell line.

摘要

间充质起源的转移性软骨肉瘤是第二常见的骨恶性肿瘤,对化疗和放疗均无反应;因此,寻找新的治疗方法既相关又迫切。本研究旨在揭示在人JJ012软骨肉瘤细胞系中,用mTORC1抑制剂、细胞抑制性抗增殖富含脯氨酸多肽(PRP-1)处理的对照样本和实验样本之间miRNA及其靶标的比较分析。对肿瘤特异性微小RNA表达谱的检测揭示了这些分子在多种癌症中广泛失调。据报道,微小RNA可作为疾病诊断和治疗的新型生物标志物,以及一类新型的癌基因和肿瘤抑制基因。mTORC 1抑制剂PRP-1导致人软骨肉瘤JJ012细胞系中肿瘤抑制因子如miR20a、miR125b和miR192显著上调;以及癌miRNA miR509-3p、miR589、miR490-3p、miR 550下调。

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