MicroRNA-19b inhibitors can attenuate the STAT3 signaling pathway in NPC C666-1 cells
MicroRNA-19b inhibitors can attenuate the STAT3 signaling pathway in NPC C666-1 cells
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MicroRNA-19b抑制剂可以减弱NPC C666-1细胞中的STAT3信号通路
DOI：
10.3892/mmr.2020.11112
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发表时间：
2020-07-01
影响因子：
3.4
通讯作者：
Xiao, Sheng-Jun
中科院分区：
文献类型：
--
作者：
Bian, Li-Hui;Duan, Jing-Ling;Xiao, Sheng-Jun
MicroRNA (miR)-19b 在多种类型的肿瘤中表达，可能作为潜在的治疗靶点。 miR-17-92 簇在鼻咽癌 (NPC) 组织和细胞中表达上调。 miR-19b是miR-17-92簇的成员；然而，其在鼻咽癌中的表达和功能很大程度上未知。本研究旨在探讨miR-19b在鼻咽癌细胞中的表达和功能。将 miRCURY LNA™ miRNA 抑制剂（miR-19b 抑制剂和阴性对照）转染至 C666-1 细胞中。随后分别通过Cell Counting Kit-8法、流式细胞术和Transwell法检测细胞的增殖、凋亡和迁移。此外，通过蛋白质印迹法检测STAT3信号通路相关蛋白[STAT3、pSTAT3和细胞因子信号传导抑制因子1 (SOCS1)]和pSTAT3转录靶标[Bcl-2、骨髓性白血病蛋白1 (Mcl-1)和细胞周期蛋白D1]的表达。 miR-19b抑制剂抑制C666-1细胞的增殖和迁移并诱导细胞凋亡。此外，miR-19b抑制剂上调了SOCS1（miR-19b的预测靶基因）的表达，并降低了STAT3 Tyr705和Ser727位点的磷酸化。这些数据表明，SOCS1（一种 STAT3 磷酸化的内源性抑制剂）的上调会减弱 C666-1 细胞中的 STAT3 信号通路。此外，转染miR-19b抑制剂后，增殖蛋白cyclin D1以及抗凋亡蛋白Mcl-1和Bcl-2的表达水平显着降低。上述三种蛋白是激活的 STAT3 信号通路的下游转录靶标。本研究的结果表明，抑制 miR-19b 通过 STAT3 信号通路负向调节鼻咽癌细胞的恶性行为。因此，抑制miR-19b可能作为鼻咽癌治疗的新靶点。
MicroRNA (miR)-19b is expressed in various types of tumors and may serve as a potential therapeutic target. The miR-17-92 cluster is upregulated in nasopharyngeal carcinoma (NPC) tissues and cells. miR-19b is a member of the miR-17-92 cluster; however, its expression and function in NPC are largely unknown. The present study aimed to investigate the expression and function of miR-19b in NPC cells. The miRCURY LNA™ miRNA Inhibitor (miR-19b inhibitor and negative control) were transfected into C666-1 cells. The proliferation, apoptosis and migration of the cells were subsequently detected by the Cell Counting Kit-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the expression of STAT3 signaling pathway-associated proteins [STAT3, pSTAT3 and suppressor of cytokine signaling 1 (SOCS1)] and the transcriptional targets of pSTAT3 [Bcl-2, myeloid leukemia protein 1 (Mcl-1) and cyclin D1] were detected by western blotting. The miR-19b inhibitor inhibited proliferation and migration and induced apoptosis of C666-1 cells. Furthermore, the miR-19b inhibitor upregulated the expression of SOCS1, a predicted target gene of miR-19b, and decreased the phosphorylation of STAT3 at Tyr705 and Ser727. These data indicated that upregulation of SOCS1, an endogenous inhibitor of STAT3 phosphorylation, attenuated the STAT3 signaling pathway in C666-1 cells. Moreover, the expression level of the proproliferative protein cyclin D1 and antiapoptotic proteins Mcl-1 and Bcl-2 was significantly decreased following transfection with the miR-19b inhibitor. The aforementioned three proteins are downstream transcriptional targets of the activated STAT3 signaling pathway. The results of the present study revealed that inhibition of miR-19b negatively modulated the malignant behavior of NPC cells via the STAT3 signaling pathway. Therefore, miR-19b inhibition may serve as a novel therapeutic target for the treatment of NPC.