Department of Traumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Hemopurification Center, Yantaiyuhuangding Hospital, Yantai, Shandong, China.
Cancer Biomark. 2017 Dec 12;21(1):135-144. doi: 10.3233/CBM-170452.
Osteosarcoma is the most common primary malignancy in bone. Patients who respond poorly to induction chemotherapy are at higher risk of adverse prognosis. The molecular basis for such poor prognosis remains unclear. Recently, increasing evidence has suggested decreased expression of miR-34a is observed in a number of cancer types, including human osteosarcoma, and decreased miR-34a is involved in drug resistance. However, the underlying molecular mechanisms of decreased miR-34a on cisplatin chemoresistance in osteosarcoma has not been reported.
Osteosarcoma U2OS cells were transfected with miR-34a mimics for 48 h, then the cells were treated with 3.0 μm cisplatin for 24 h. Using siRNA targeting c-Myc and Bim to examine the relation between miR-34a, c-Myc and Bim expression exposure to cisplatin on cisplatin-induced apoptosis.
Treatment of U2OS cells with cisplatin induced cell apoptosis by upregulation of c-Myc -dependent Bim expression; Osteosarcoma U2OS cells transfected with miR-34a mimics (miR-34a/U2OS) induced cell apoptosis and inhibited cell survival, and increased the sensitivity of U2OS cells to cisplatin. U2OS cells transfected with miR-34a mimics upregulated the protein expression of c-Myc and Bim. Targeting c-Myc downregulated the expression of Bim in the miR-34a/U2OS cells. In addition, Targeting Bim reversed the chemeresistance of miR-34a/U2OS cells to cisplatin.
Our data indicated that miR-34a enhanced the sensitivity to cisplatin by upregulation of c-Myc and Bim pathway.
骨肉瘤是最常见的原发性骨恶性肿瘤。对诱导化疗反应不佳的患者预后不良风险较高。这种不良预后的分子基础尚不清楚。最近，越来越多的证据表明，miR-34a 在多种癌症类型中表达降低，包括骨肉瘤，并且降低的 miR-34a 参与了耐药性。然而，骨肉瘤中 miR-34a 降低对顺铂化疗耐药性的潜在分子机制尚未报道。
用 miR-34a 模拟物转染骨肉瘤 U2OS 细胞 48 小时，然后用 3.0 μm 顺铂处理 24 小时。用靶向 c-Myc 和 Bim 的 siRNA 检测 miR-34a、c-Myc 和 Bim 表达与顺铂诱导凋亡之间的关系。
顺铂处理 U2OS 细胞通过上调 c-Myc 依赖性 Bim 表达诱导细胞凋亡；转染 miR-34a 模拟物的骨肉瘤 U2OS 细胞（miR-34a/U2OS）诱导细胞凋亡并抑制细胞存活，并增加 U2OS 细胞对顺铂的敏感性。转染 miR-34a 模拟物的 U2OS 细胞上调了 c-Myc 和 Bim 的蛋白表达。靶向 c-Myc 下调了 miR-34a/U2OS 细胞中 Bim 的表达。此外，靶向 Bim 逆转了 miR-34a/U2OS 细胞对顺铂的耐药性。
我们的数据表明，miR-34a 通过上调 c-Myc 和 Bim 通路增强了对顺铂的敏感性。
