MiR-125b regulates proliferation and apoptosis of nasopharyngeal carcinoma by targeting A20/NF-κB signaling pathway.
MiR-125b regulates proliferation and apoptosis of nasopharyngeal carcinoma by targeting A20/NF-κB signaling pathway.
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MiR-125b通过靶向A20/NF-κB信号通路调控鼻咽癌增殖和凋亡
DOI：
10.1038/cddis.2017.211
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发表时间：
2017-06-01
影响因子：
9
通讯作者：
Xiao ZQ
中科院分区：
文献类型：
--
作者：
Zheng Z;Qu JQ;Yi HM;Ye X;Huang W;Xiao T;Li JY;Wang YY;Feng J;Zhu JF;Lu SS;Yi H;Xiao ZQ
MiR-125b异常表达，并在各种类型的肿瘤中发挥作用。然而，miR-125b在鼻咽癌（NPC）中的作用和机制尚不清楚。在本研究中，我们探讨了miR-125b在鼻咽癌中的作用和机制。我们观察到，相对于正常鼻咽黏膜（NNM）， miR-125b在鼻咽癌组织中显著上调，其升高与患者生存率低相关，是患者生存率降低的独立预测因子；miR-125b促进鼻咽癌细胞增殖，抑制鼻咽癌细胞凋亡；在小鼠模型中，miR-125b拮抗剂可显著降低鼻咽癌异种移植肿瘤的生长。在机制上，我们证实A20是miR-125b的直接靶点，并发现A20激活核因子κB （NF-κB）信号通路介导miR-125b促进鼻咽癌细胞增殖，抑制鼻咽癌细胞凋亡。通过功能丧失和功能获得相结合的方法，我们进一步发现A20抑制鼻咽癌细胞增殖，诱导鼻咽癌细胞凋亡，并降低鼻咽癌异种移植肿瘤的生长。此外，相对于正常鼻咽黏膜，鼻咽癌组织中A20显著下调，而p-p65（RelA）显著上调，miR-125b水平与A20水平呈负相关，而与p-p65水平呈正相关。我们的数据表明，miR-125b通过靶向A20/NF-κB信号通路调控鼻咽癌细胞增殖和凋亡，miR-125b在鼻咽癌中作为癌基因，而A20在鼻咽癌中作为抑癌基因，突出了miR-125b/A20/NF-κB信号轴在鼻咽癌中的治疗潜力。
MiR-125b is aberrantly expressed and has a role in the various types of tumors. However, the role and mechanism of miR-125b in nasopharyngeal carcinoma (NPC) are unclear. In this study, we investigated the role and mechanism of miR-125b in NPC. We observed that miR-125b was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM), and its increment was correlated with poor patient survival, and was an independent predictor for reduced patient survival; miR-125b promoted NPC cell proliferation and inhibited NPC cell apoptosis; in a mouse model, administration of miR-125b antagomir significantly reduced the growth of NPC xenograft tumors. Mechanistically, we confirmed that A20 was a direct target of miR-125b, and found that activation of nuclear factor κB (NF-κB) signaling pathway by A20 mediated miR-125b-promoting NPC cell proliferation and -inhibiting NPC cell apoptosis. With a combination of loss-of-function and gain-of-function approaches, we further showed that A20 inhibited NPC cell proliferation, induced NPC cell apoptosis, and reduced the growth of NPC xenograft tumors. Moreover, A20 was significantly downregulated, whereas p-p65(RelA) was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa, and miR-125b level was negatively associated with A20 level, whereas positively associated with p-p65 level. Our data demonstrate that miR-125b regulates NPC cell proliferation and apoptosis by targeting A20/NF-κB signaling pathway, and miR-125b acts as oncogene, whereas A20 functions as tumor suppressor in NPC, highlighting the therapeutic potential of miR-125b/A20/NF-κB signaling axis in the NPC.
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DOI：
10.1002/hed.20833
发表时间：
2008-07
影响因子：
2.9
作者：
Chou, Josephine;Lin, Yu-Ching;Kim, Jae;You, Liang;Xu, Zhidong;He, Biao;Jablons, David M.
通讯作者：
Jablons, David M.
TNFAIP3（A20）是霍奇金淋巴瘤和原发性纵隔B细胞淋巴瘤中的肿瘤抑制基因。
DOI：
10.1084/jem.20090528
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Schmitz R;Hansmann ML;Bohle V;Martin-Subero JI;Hartmann S;Mechtersheimer G;Klapper W;Vater I;Giefing M;Gesk S;Stanelle J;Siebert R;Küppers R
通讯作者：
Küppers R
影响因子：
64.8
作者：
Compagno, Mara;Lim, Wei Keat;Grunn, Adina;Nandula, Subhadra V.;Brahmachary, Manisha;Shen, Qiong;Bertoni, Francesco;Ponzoni, Maurilio;Scandurra, Marta;Califano, Andrea;Bhagat, Govind;Chadburn, Amy;Dalla-Favera, Riccardo;Pasqualucci, Laura
通讯作者：
Pasqualucci, Laura
影响因子：
7.3
作者：
Chung, Grace Tin-Yun;Lou, Wilson Pak-Kin;Lo, Kwok-Wai
通讯作者：
Lo, Kwok-Wai
通过蛋白质组学鉴定预测鼻咽癌放疗反应的生物标志物
影响因子：
11.2
作者：
Feng, Xue-Ping;Yi, Hong;Xiao, Zhi-Qiang
通讯作者：
Xiao, Zhi-Qiang