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微小RNA与骨癌

microRNA and Bone Cancer.

作者信息

Nugent Mary

机构信息

Department of Trauma and Orthopaedics, St. James Hospital, Dublin 8, Ireland.

出版信息

Adv Exp Med Biol. 2015;889:201-30. doi: 10.1007/978-3-319-23730-5_11.

Abstract

MicroRNA molecules have a variety of roles in cellular development and proliferation processes, including normal osteogenesis. These effects are exerted through post-translational inhibition of target genes. Altered miRNA expression has been demonstrated in several cancers, both in the tumor tissue and in the peripheral circulation. This may influence carcinogenesis if the specific miRNA targets are encoded by tumor suppressor genes or oncogenes. To date, most research investigating the role of microRNAs and primary bone tumors has focused on osteosarcoma and Ewing sarcoma. Several microRNAs including the miR-34 family have been implicated in osteosarcoma tumorigenesis via effects on the Notch signaling pathway. Progression, invasion, and metastasis of osteosarcoma tumor cells is also influenced by microRNA expression. In addition, microRNA expression may affect the response to chemotherapy in osteosarcoma and thus hold potential for future use as either a prognostic indicator or a therapeutic target. The EWS-FLI1 fusion protein produced in Ewing sarcoma has been shown to induce changes in miRNA expression. MicroRNA expression profiling may have some potential for prediction of disease progression and survival in Ewing sarcoma. There is limited evidence to support a role for microRNAs in other primary bone tumors, either malignant or benign; however, early work is suggestive of involvement in chondrosarcoma, multiple osteochondromatosis, and giant cell tumors of bone.

摘要

微小RNA分子在细胞发育和增殖过程中发挥着多种作用,包括正常的骨生成。这些作用是通过对靶基因的翻译后抑制来实现的。在几种癌症中,无论是肿瘤组织还是外周循环中,都已证实微小RNA表达发生了改变。如果特定的微小RNA靶标由肿瘤抑制基因或癌基因编码,这可能会影响肿瘤发生。迄今为止,大多数研究微小RNA与原发性骨肿瘤作用的研究都集中在骨肉瘤和尤因肉瘤上。包括miR-34家族在内的几种微小RNA已通过对Notch信号通路的影响而与骨肉瘤的肿瘤发生有关。骨肉瘤肿瘤细胞的进展、侵袭和转移也受微小RNA表达的影响。此外,微小RNA表达可能会影响骨肉瘤对化疗的反应,因此有望在未来用作预后指标或治疗靶点。尤因肉瘤中产生的EWS-FLI1融合蛋白已被证明可诱导微小RNA表达的变化。微小RNA表达谱分析在预测尤因肉瘤的疾病进展和生存方面可能具有一定潜力。支持微小RNA在其他原发性骨肿瘤(无论是恶性还是良性)中发挥作用的证据有限;然而,早期研究表明其与软骨肉瘤、多发性骨软骨瘤病和骨巨细胞瘤有关。

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