miR-374a-CCND 1-pPI3KJAKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin
miR-374a-CCND 1-pPI3KJAKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin
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PDCD4 调节的 miR-374a-CCND1-pPI3K/AKT-c-JUN 反馈环路可抑制细胞生长、转移，并使鼻咽癌对顺铂敏感。
DOI：
10.1038/onc.2016.201
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发表时间：
2017-01-12
期刊：
影响因子：
8
通讯作者：
Liu, Z.
中科院分区：
文献类型：
--
作者：
Zhen, Y.;Fang, W.;Liu, Z.
据报道，miR-374 a在肿瘤发病过程中作为癌基因发挥作用。在本研究中，观察到miR-374 a在体外和体内降低鼻咽癌（NPC）细胞的增殖、迁移、侵袭、转移和顺铂（DDP）耐药性。机制分析表明，miR-374 a直接将CCND 1靶向于pPI 3 K/pAKT/c-JUN，形成负反馈环，并抑制与细胞周期进展和上皮-间质转化（EMT）相关的下游信号。有趣的是，我们还观察到miR-374 a直接靶向CCND 1通过抑制pPI 3 K/pAKT/c-JUN信号转导被肿瘤抑制因子PDCD 4调节。在临床标本中，miR-374 a分别与PDCD 4和CCND 1的表达呈正相关和负相关。我们的研究首次证明了PDCD 4诱导的miR-374 a-CCND 1-pPI 3 K/AKT-c-JUN反馈环抑制NPC细胞的生长、转移和化疗耐药性。
miR-374a has been reported to function as an oncogene during tumor pathogenesis. In this study, miR-374a is observed to reduce nasopharyngeal carcinoma (NPC) cell proliferation, migration, invasion, metastasis and cisplatin (DDP) resistance in vitro and in vivo. Mechanistic analyses indicate that miR-374a directly targets CCND1 to inactivate pPI3K/pAKT/c-JUN forming a negative feedback loop, as well as suppressing downstream signals related to cell cycle progression and epithelial− mesenchymal transition (EMT). Interestingly, we also observed that miR-374a direct targeting of CCND1 is modulated by tumor suppressor PDCD4 via suppressing pPI3K/pAKT/c-JUN signaling. In clinical specimens, miR-374a was positively and negatively correlated with expression of PDCD4 and CCND1, respectively. Our studies are the first to demonstrate that the miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop induced by PDCD4 supresses NPC cell growth, metastasis and chemotherapy resistance.