MicroRNA-372 enhances radiosensitivity while inhibiting cell invasion and metastasis in nasopharyngeal carcinoma through activating the PBK-dependent p53 signaling pathway
MicroRNA-372 enhances radiosensitivity while inhibiting cell invasion and metastasis in nasopharyngeal carcinoma through activating the PBK-dependent p53 signaling pathway
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MicroRNA-372通过激活PBK依赖性p53信号通路增强放射敏感性，同时抑制鼻咽癌细胞侵袭和转移
DOI：
10.1002/cam4.1924
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发表时间：
2019-02-01
期刊：
影响因子：
4
通讯作者：
Wang, Ruo-Yu
中科院分区：
文献类型：
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作者：
Wang, Zhe;Mao, Ji-Wei;Wang, Ruo-Yu
鼻咽癌是鼻咽部常见的癌症，困扰着无数鼻咽癌患者。MicroRNA-372(miR-372)已被报道参与多种肿瘤的发生。在这里，我们探讨miR-372在鼻咽癌放射敏感性、侵袭和转移中的重要作用。基因芯片分析寻找鼻咽癌相关差异表达基因(Degs)，预测miR-372可能通过pBK和P53信号通路影响鼻咽癌的发生发展。重要的是，观察到miR-372靶向PBK，从而下调其表达。然后选择鼻咽癌5-8F和C666-1细胞，用电离辐射和miR-372及PBK表达的改变来探讨miR-372在鼻咽癌中的功能作用。检测miR-372、PBK、Bcl2、P53、Bax的表达及Akt的磷酸化程度。此外，还检测了细胞集落形成、细胞周期、增殖、凋亡、迁移和侵袭。最后评价肿瘤生长情况及miR-372对鼻咽癌放射增敏的影响。此外，miR-372过表达下调了Bcl2和PBK的表达，下调了Akt的磷酸化程度，上调了P53和Bax的表达。此外，miR-372过表达和放射治疗抑制细胞克隆形成、增殖、肿瘤生长、迁移、侵袭和细胞周期进入，但促进细胞凋亡。然而，在表达miR-372的鼻咽癌细胞中，PBK的恢复逆转了miR-372的抗肿瘤作用和P53信号通路的激活。总之，研究表明，上调的miR-372通过抑制PBK激活P53信号通路来促进放射敏感性。
Nasopharyngeal carcinoma (NPC) is a common cancer found in the nasopharynx, which plagues countless NPC patients. MicroRNA-372 (miR-372) has been reported to be involved in various tumors. Here, we explored the important role of miR-372 in radiosensitivity, invasion, and metastasis of NPC. Microarray analysis was conducted to search the NPC-related differentially expressed genes (DEGs) and predict the miRs regulating PBK, which suggested that miR-372 could influence the development of NPC via PBK and the p53 signaling pathway. Importantly, miR-372 was observed to target PBK, thus down-regulating its expression. Then, NPC 5-8F and C666-1 cells were selected, and treated with ionization radiation and alteration of miR-372 and PBK expression to explore the functional role of miR-372 in NPC. The expression of miR-372, PBK, Bcl-2, p53, and Bax as well as the extent of Akt phosphorylation were measured. In addition, cell colony formation, cell cycle, proliferation, apoptosis, migration, and invasion were detected. At last, tumor growth and the effect of miR-372 on radiosensitivity of NPC were evaluated. Besides, over-expressed miR-372 down-regulated Bcl-2 and PBK expression and the extent of Akt phosphorylation while up-regulated the expression of p53 and Bax. Additionally, miR-372 over-expression and radiotherapy inhibited cell clone formation, proliferation, tumor growth, migration, invasion, and cell cycle entry, but promoted cell apoptosis. However, the restoration of PBK in NPC cells expressing miR-372 reversed the anti-tumor effect of miR-372 and activation of the p53 signaling pathway. In conclusion, the study shows that up-regulated miR-372 promotes radiosensitivity by activating the p53 signaling pathway via inhibition of PBK.