长链非编码RNA在骨肉瘤中的应用:生物标志物与治疗靶点

Application of Long Noncoding RNAs in Osteosarcoma: Biomarkers and Therapeutic Targets.

作者信息

Li Zhihong, Dou Pengcheng, Liu Tang, He Shasha

机构信息

Department of Orthopaedics, the Second Xiangya Hospital, Central South University, Changsha, China.

Department of Oncology, the Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Cell Physiol Biochem. 2017;42(4):1407-1419. doi: 10.1159/000479205. Epub 2017 Jul 17.

Abstract

Osteosarcoma is the most common primary bone malignancy in children and adolescents. Although improvements in therapeutic strategies were achieved, the outcome remains poor for most patients with metastatic or recurrent osteosarcoma. Therefore, it is imperative to identify novel and effective prognostic biomarker and therapeutic targets for the disease. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts >200 nucleotides that lack protein coding potential. Many lncRNAs are deregulated in cancer and are important regulators for malignancies. Nine lncRNAs (91H, BCAR4, FGFR3-AS1, HIF2PUT, HOTTIP, HULC, MALAT-1, TUG1, UCA1) are upregulated and considered oncogenic for osteosarcoma. Loc285194 and MEG3 are two lncRNAs downregulated and as tumor suppressor for the disease. Moreover, the expressions of LINC00161 and ODRUL are associated with chemo-resistance of osteosarcoma. The mechanisms for these lncRNAs in regulating development of osteosarcoma are diverse, e.g. ceRNA, Wnt/β-catenin pathway, etc. The lncRNAs identified may serve as potential biomarkers or therapeutic targets for osteosarcoma.

摘要

骨肉瘤是儿童和青少年中最常见的原发性骨恶性肿瘤。尽管治疗策略有所改进,但大多数转移性或复发性骨肉瘤患者的预后仍然很差。因此,必须为该疾病确定新的有效预后生物标志物和治疗靶点。长链非编码RNA(lncRNA)是一类新的RNA分子,定义为长度大于200个核苷酸且缺乏蛋白质编码潜力的转录本。许多lncRNA在癌症中表达失调,是恶性肿瘤的重要调节因子。九种lncRNA(91H、BCAR4、FGFR3-AS1、HIF2PUT、HOTTIP、HULC、MALAT-1、TUG1、UCA1)在骨肉瘤中上调,并被认为具有致癌性。Loc285194和MEG3是两种下调的lncRNA,在该疾病中起肿瘤抑制作用。此外,LINC00161和ODRUL的表达与骨肉瘤的化疗耐药性相关。这些lncRNA调节骨肉瘤发生发展的机制多种多样,例如ceRNA、Wnt/β-连环蛋白途径等。已鉴定出的lncRNA可能作为骨肉瘤的潜在生物标志物或治疗靶点。

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