NR2F2 regulates bone marrow-derived mesenchymal stem cell-promoted proliferation of Reh cells.
NR2F2 regulates bone marrow-derived mesenchymal stem cell-promoted proliferation of Reh cells.
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DOI：
10.3892/mmr.2016.5389
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Ni Zhu;Huafang Wang;Jieping Wei;Binsheng Wang;W. Shan;X. Lai;Yanmin Zhao;Jian Yu;He Huang
中科院分区：
文献类型：
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作者：
Ni Zhu;Huafang Wang;Jieping Wei;Binsheng Wang;W. Shan;X. Lai;Yanmin Zhao;Jian Yu;He Huang
骨髓间充质干细胞（BM-MSCs）是白血病微环境的关键组成部分。BM-MSC先前已被报道促进白血病细胞的增殖。为了进一步了解骨髓间充质干细胞诱导白血病细胞增殖的分子机制，本研究将骨髓间充质干细胞与急性淋巴细胞白血病（ALL）Reh细胞共培养。本研究采用的方法包括shRNA、流式细胞术、MTT、逆转录-定量聚合酶链反应、ELISA和Western印迹。本研究的数据表明，BM-MSCs促进Reh细胞的增殖，并且在共培养后BM-MSCs中NR 2F 2 mRNA和蛋白水平升高。此外，研究表明，NR 2F 2的shRNA敲低抑制了BM-MSC诱导的Reh细胞增殖。此外，在NR 2F 2下调后，BM-MSCs的血管内皮生长因子A（VEGFA）分泌减少。目前的研究表明，NR 2F 2介导BM-MSC诱导的Reh细胞增殖，部分通过调节VEGFA。通过靶向NR 2F 2破坏微环境支持可能是ALL的潜在治疗策略。
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are pivotal components of the leukemic microenvironment. BM-MSCs have been previously reported to promote the proliferation of leukemic cells. To further understand the molecular mechanisms of BM-MSC-induced proliferation of leukemic cells, the present study co-cultured acute lymphoblastic leukemia (ALL) Reh cells with BM-MSCs. The current study used methods including shRNA, flow cytometry, MTT, reverse transcription-quantitative polymerase chain reaction, ELISA and western blotting. The data of the present study demonstrated that BM‑MSCs promote the proliferation of Reh cells and the NR2F2 mRNA and protein levels were elevated in BM‑MSCs following co‑culture. Additionally, it was demonstrated that shRNA knockdown of NR2F2 inhibited BM‑MSC‑induced proliferation of Reh cells. Furthermore, following downregulation of NR2F2, vascular endothelial growth factor A (VEGFA) secretion by BM‑MSCs was reduced. The present study demonstrated that NR2F2 mediates BM‑MSC‑induced proliferation of Reh cells, partially via regulation of VEGFA. Disrupting microenvironmental support by targeting NR2F2 may be a potential therapeutic strategy for ALL.