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miR-15a 通过靶向和下调人骨肉瘤细胞中 Bcl-2 的表达来抑制低氧条件下的癌细胞迁移和侵袭。

miR‑15a represses cancer cell migration and invasion under conditions of hypoxia by targeting and downregulating Bcl‑2 expression in human osteosarcoma cells.

机构信息

Nursing Platform of Bone, Joint and Sports Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Int J Oncol. 2018 Apr;52(4):1095-1104. doi: 10.3892/ijo.2018.4285. Epub 2018 Feb 23.

DOI:10.3892/ijo.2018.4285
PMID:29484432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5843390/
Abstract

Osteosarcoma is a common, high-risk primary bone malignancy that mostly affects the younger population. There has been no marked improvement in the clinical outcomes of osteosarcoma patients to date, and cancer recurrence and metastasis are common in high-grade osteosarcoma. Therefore, identifying new biomarkers and novel therapeutic targets is crucial for improving the prognosis of osteosarcoma patients. In the present study, the MG63 human osteosarcoma cell line was employed to examine the role of microRNA (miR)‑15a in regulating cellular activities under hypoxic conditions. It was demonstrated that hypoxia stimulates migration and invasion in MG63 cells, which was correlated with the downregulation of miR‑15a and upregulation of B-cell lymphoma 2 (Bcl‑2) expression. Introduction of miR‑15a or knockdown of endogenous Bcl‑2 may reduce hypoxia-induced cell invasion and migration through the regulation of matrix metalloproteinases. Analysis of the expression of miR‑15a indicated that hypoxia repressed the transcription of deleted in lymphocytic leukemia 2 (DLEU2), which is the host gene of miR‑15a. These findings indicated that miR‑15a may be a valuable target for the treatment of osteosarcoma, particularly for patients with high-grade cancer or heavy tumor burden.

摘要

骨肉瘤是一种常见的、高风险的原发性骨恶性肿瘤,主要影响年轻人群。迄今为止,骨肉瘤患者的临床结局并未有明显改善,而癌症复发和转移在高级别骨肉瘤中很常见。因此,确定新的生物标志物和新的治疗靶点对于改善骨肉瘤患者的预后至关重要。在本研究中,使用 MG63 人骨肉瘤细胞系来研究 microRNA(miR)-15a 在缺氧条件下调节细胞活性的作用。结果表明,缺氧刺激 MG63 细胞的迁移和侵袭,这与 miR-15a 的下调和 B 细胞淋巴瘤 2(Bcl-2)表达的上调相关。miR-15a 的引入或内源性 Bcl-2 的敲低可能通过调节基质金属蛋白酶来减少缺氧诱导的细胞侵袭和迁移。miR-15a 表达的分析表明,缺氧抑制了Deleted in Lymphocytic Leukemia 2(DLEU2)的转录,DLEU2 是 miR-15a 的宿主基因。这些发现表明,miR-15a 可能是治疗骨肉瘤的一个有价值的靶点,特别是对于高级别癌症或肿瘤负荷较重的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/5316fdbf5d35/IJO-52-04-1095-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/1a58fb0ec606/IJO-52-04-1095-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/836834d85e4b/IJO-52-04-1095-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/40d2be297520/IJO-52-04-1095-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/d0c0575e5222/IJO-52-04-1095-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/11801bab6ddf/IJO-52-04-1095-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/5316fdbf5d35/IJO-52-04-1095-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/1a58fb0ec606/IJO-52-04-1095-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/836834d85e4b/IJO-52-04-1095-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/40d2be297520/IJO-52-04-1095-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/d0c0575e5222/IJO-52-04-1095-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/11801bab6ddf/IJO-52-04-1095-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49dd/5843390/5316fdbf5d35/IJO-52-04-1095-g05.jpg

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