miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4.

miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4.
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miR-181b 通过靶向 PDCD4 作为结直肠癌中的 oncomiR

DOI:
10.1007/s13238-016-0313-2
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发表时间:
2016-10
期刊:
影响因子:
21.1
通讯作者:
Chen, Xi
Chen, Xi
中科院分区:
生物学1区
文献类型:
--
作者:
Liu, Yanqing;Uzair-ur-Rehman;Guo, Yu;Liang, Hongwei;Cheng, Rongjie;Yang, Fei;Hong, Yeting;Zhao, Chihao;Liu, Minghui;Yu, Mengchao;Zhou, Xinyan;Yin, Kai;Chen, Jiangning;Zhang, Junfeng;Zhang, Chen-Yu;Zhi, Feng;Chen, Xi

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程序性细胞死亡4(PDCD4)是一种RNA结合蛋白,在许多癌症类型中发挥肿瘤抑制作用,包括结直肠癌(CRC)。在结直肠癌发生过程中,PDCD4蛋白水平显著降低,但其表达降低的分子机制尚不完全清楚。在这项研究中,我们进行了生物信息学分析,以确定潜在的靶向PDCD4的miRNAs。我们证明了miR-181b是PDCD4的直接调节因子。我们进一步表明,IL6/STAT3信号通路的激活增加了miR-181b的表达,从而导致了结直肠癌细胞中PDCD4的下调。此外,我们还研究了miR-181b体外和活体抑制PDCD4的生物学效应,发现miR-181b可能通过靶向PDCD4而促进肿瘤细胞的增殖和迁移,抑制肿瘤细胞的凋亡,促进移植瘤的生长。综上所述,这项研究强调了miR-181b在调节结直肠癌PDCD4中的肿瘤作用,并提示miR-181b可能是结直肠癌的一个新的分子治疗靶点。
Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b bothin vitroandin vivoand found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.
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影响因子: --
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