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在骨肉瘤中,miR-125a-5p的下调通过直接靶向基质金属蛋白酶11(MMP-11)发挥肿瘤抑制作用。

The downregulation of miR‑125a‑5p functions as a tumor suppressor by directly targeting MMP‑11 in osteosarcoma.

作者信息

Waresijiang Niyazi, Sun Jungang, Abuduaini Rewuti, Jiang Tayier, Zhou Wenzheng, Yuan Hong

机构信息

Department of Orthopaedics, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China.

出版信息

Mol Med Rep. 2016 Jun;13(6):4859-64. doi: 10.3892/mmr.2016.5141. Epub 2016 Apr 15.

Abstract

Osteosarcoma is one of the most common primary malignant bone cancers in juveniles and adults. Increasingly, reports indicate that microRNAs (miRNAs) may provide novel therapeutic targets for cancer treatment. The aim of the present study was to investigate the expression of miR‑125a‑5p and to identify its functional significance in osteosarcoma. This indicated that miR‑125a‑5p was downregulated in osteosarcoma tissue and cell lines using reverse transcription‑quantitative polymerase chain reaction. Following transfection with miR‑125a‑5p mimics or the negative control, cell migration, invasion and epithelial‑mesenchymal transition (EMT) assays were conducted in osteosarcoma cells. These results indicated that the overexpression of miR‑125a‑5p resulted in inhibited osteosarcoma cell migration, invasion and EMT in vitro. Furthermore, mechanistic studies showed that matrix metallopeptidase‑11 (MMP‑11), was a direct target of miR‑125a‑5p in osteosarcoma. Taken together, the data demonstrate that miR‑125a‑5p functions as a tumor suppressor gene and serves an important role in inhibiting osteosarcoma cell migration, invasion and EMT by targeting MMP‑11.

摘要

骨肉瘤是青少年和成年人中最常见的原发性恶性骨癌之一。越来越多的报道表明,微小RNA(miRNA)可能为癌症治疗提供新的治疗靶点。本研究的目的是调查miR-125a-5p的表达,并确定其在骨肉瘤中的功能意义。逆转录-定量聚合酶链反应结果表明,miR-125a-5p在骨肉瘤组织和细胞系中表达下调。用miR-125a-5p模拟物或阴性对照转染后,对骨肉瘤细胞进行细胞迁移、侵袭和上皮-间质转化(EMT)检测。这些结果表明,miR-125a-5p的过表达导致体外骨肉瘤细胞迁移、侵袭和EMT受到抑制。此外,机制研究表明,基质金属蛋白酶-11(MMP-11)是骨肉瘤中miR-125a-5p的直接靶点。综上所述,数据表明miR-125a-5p作为一种肿瘤抑制基因,通过靶向MMP-11在抑制骨肉瘤细胞迁移、侵袭和EMT中发挥重要作用。

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