MicroRNA-294 Promotes Cellular Proliferation and Motility through the PI3K/AKT and JAK/STAT Pathways by Upregulation of NRAS in Bladder Cancer
MicroRNA-294 Promotes Cellular Proliferation and Motility through the PI3K/AKT and JAK/STAT Pathways by Upregulation of NRAS in Bladder Cancer
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MicroRNA-294 通过上调 NRAS 在膀胱癌中通过 PI3K/AKT 和 JAK/STAT 途径促进细胞增殖和运动
DOI：
10.1134/s0006297917040095
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发表时间：
2017-04-01
影响因子：
2.8
通讯作者：
Xu, Yankai
中科院分区：
文献类型：
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作者：
Li, Yongwei;Shan, Zhengfei;Xu, Yankai
在我们的研究中，我们研究了microRNA-294 （miR-294）在膀胱癌中的作用及其相关机制。采用实时聚合酶链反应（RT-PCR）检测miR-294的表达水平。Western blot检测NRAS的表达，主要是PI3K/AKT和JAK/STAT通路的因子。采用细胞计数kit8法、克隆生成法、创面愈合法、transwell法和流式细胞术分别检测膀胱癌细胞株T24的细胞增殖、存活、迁移、侵袭和凋亡情况。miR-294在包括J82、HT1376、T24和SW780在内的膀胱癌细胞中的表达比在人膀胱上皮细胞（HCV29和SV-HUC-1）中的表达显著升高。转染miR-294 inhibitor组T24细胞的增殖率、存活率、迁移率和侵袭率均显著升高，转染miR-294 inhibitor组T24细胞的增殖率、存活率、迁移率和侵袭率均显著降低。抑制miR-294可提高T24细胞的凋亡率。此外，miR-294模拟物治疗组T24细胞对顺铂的耐药性增加，miR-294抑制剂治疗组与空对照组相比，T24细胞对顺铂的耐药性降低。过表达miR-294可上调T24细胞中NRAS的表达，激活PI3K/AKT和JAK/STAT通路。我们发现miR-294的表达与T24细胞的增殖和运动性呈正相关。此外，miR-294抑制可促进T24细胞对顺铂的敏感性。我们还发现miR-294可以上调NRAS并激活T24细胞中的PI3K/AKT和JAK/STAT通路。
In our study we examined the role of microRNA-294 (miR-294) in bladder cancer and related mechanisms. Realtime polymerase chain reaction (RT-PCR) was performed to determine the expression level of miR-294. Western blot was used to determine the expression of NRAS, mainly factors in the PI3K/AKT and JAK/STAT pathways. Cell counting kit8 assay, clonogenic assay, wound-healing assay, transwell and flow cytometry were used to explore, respectively, cell proliferation, survival, migration, invasion, and apoptosis of bladder cancer cell line T24. The expressions of miR-294 in bladder cancer cells including J82, HT1376, T24, and SW780 were significantly increased compared to those in human bladder epithelium cells (both HCV29 and SV-HUC-1). The proliferation rate, surviving fraction, migration, and invasion of T24 cells in miR-294 mimetic transfected group were significantly increased, while they were significantly decreased by miR294 inhibitor transfection. Moreover, miR-294 suppression could increase the apoptotic rate of T24 cells. In addition, drug resistance of T24 cells to cisplatin was increased in miR-294 mimetic-treated group, while it was decreased by miR-294 inhibitor compared to empty control. Overexpression of miR-294 could upregulate NRAS expression in T24 cells and activate PI3K/AKT and JAK/STAT pathways. We found that miR-294 expression was positively related with proliferation and motility of T24 cells. Moreover, miR-294 suppression could promote the sensitivity of T24 cells to cisplatin. We also found miR-294 could upregulate NRAS and activate the PI3K/AKT and JAK/STAT pathways in T24 cells.