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微小RNA-214通过直接靶向磷酸酶和张力蛋白同源物来调节骨肉瘤的存活和生长。

MicroRNA-214 regulates osteosarcoma survival and growth by directly targeting phosphatase and tensin homolog.

作者信息

Wang Xuming, Sun Jiabing, Fu Chunjiang, Wang Dewei, Bi Zhenggang

机构信息

Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Mol Med Rep. 2014 Dec;10(6):3073-9. doi: 10.3892/mmr.2014.2616. Epub 2014 Oct 9.

Abstract

An increasing number of microRNAs (miRNAs) have been identified as diagnostic and prognostic biomarkers, as well as additional therapeutic tools, in skeletal diseases. Recent studies have established the pathophysiological role of miR‑214, using human osteoporotic bone specimens. However, miR‑214 expression levels and the underlying regulatory mechanism in human osteosarcoma remain unclear. Quantitative polymerase chain reaction (qPCR) was used to examine the expression of miR‑214 in human osteosarcoma tissues and cells. Transfection of the cells with either a miR‑214 expressing‑plasmid, mimic or inhibitor was performed, in order to investigate the role of miR‑214 in osteosarcoma. In this study, miR‑214 was shown to be significantly increased in the majority of 15 examined osteosarcoma tissues and in the Saos‑2 human osteosarcoma cell line. Overexpression of miR‑214 in Saos‑2 cells induced cell proliferation, while inhibition of miR‑214 promoted Saos‑2 cell apoptosis in vitro. Furthermore, ectopic expression of miR‑214 markedly promoted osteosarcoma development in a subcutaneous xenotransplantation model in BALB/c athymic nude mice. The role of miR‑214 in osteocarcinogenesis was further investigated and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR‑214 in Saos‑2 cells. The proliferation‑promoting effect of PTEN knockdown was similar to that of miR‑214 overexpression. This study revealed that miR‑214 exerted a crucial role in promoting osteosarcoma progression and this suggests that modulation of miR‑214 levels may provide a novel therapeutic approach in cancer treatment.

摘要

越来越多的微小RNA(miRNA)已被确定为骨骼疾病中的诊断和预后生物标志物以及额外的治疗工具。最近的研究利用人类骨质疏松骨标本确定了miR-214的病理生理作用。然而,miR-214在人类骨肉瘤中的表达水平及其潜在调控机制仍不清楚。采用定量聚合酶链反应(qPCR)检测miR-214在人类骨肉瘤组织和细胞中的表达。为了研究miR-214在骨肉瘤中的作用,对细胞进行了miR-214表达质粒、模拟物或抑制剂的转染。在本研究中,miR-214在15个检测的骨肉瘤组织中的大多数以及Saos-2人骨肉瘤细胞系中显著升高。miR-214在Saos-2细胞中的过表达诱导细胞增殖,而miR-214的抑制则促进体外Saos-2细胞凋亡。此外,miR-214的异位表达在BALB/c无胸腺裸鼠的皮下异种移植模型中显著促进骨肉瘤发展。进一步研究了miR-214在骨肉瘤发生中的作用,并确定磷酸酶和张力蛋白同源物(PTEN)是Saos-2细胞中miR-214的直接靶点。PTEN敲低的促增殖作用与miR-214过表达相似。本研究表明,miR-214在促进骨肉瘤进展中发挥关键作用,这表明调节miR-214水平可能为癌症治疗提供一种新的治疗方法。

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