CPEB3 functions as a tumor suppressor in colorectal cancer via JAK/STAT signaling.
CPEB3 functions as a tumor suppressor in colorectal cancer via JAK/STAT signaling.
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CPEB3 通过 JAK/STAT 信号传导在结直肠癌中发挥肿瘤抑制因子的作用
DOI：
10.18632/aging.103893
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发表时间：
2020-11-03
期刊：
影响因子：
--
通讯作者：
Yan Q
中科院分区：
文献类型：
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作者：
Fang Y;Zhong Q;Wang Y;Gu C;Liu S;Li A;Yan Q
胞质多聚腺苷酸化元件结合蛋白（CPEBs）作为RNA结合蛋白，通过转录后调节调控恶性转化相关基因的表达，已引起人们的广泛关注。然而，CPEB 3对癌症恶性发展的贡献知之甚少。在这项研究中，我们探讨了CPEB 3在结直肠癌进展中的临床，生物学和机械作用。我们发现结直肠癌组织表现出CPEB 3表达减弱，这与结直肠癌患者的不良预后密切相关（47个月对62个月，P = 0.035，n=99）。下调CPEB 3促进结直肠癌细胞的增殖、迁移和侵袭，反之亦然。机制上，CPEB 3作为RNA结合蛋白与JAK 1 mRNA的3个UTR结合，以抑制结直肠癌细胞中的JAK/STAT通路。CPEB 3的敲低诱导了JAK-STAT信号的激活，从而触发了结直肠癌细胞的增殖和转移能力。这些结果表明，CPEB 3通过其JAK/STAT信号的转录后调节在结直肠癌中作为肿瘤抑制因子发挥作用。含义：这项研究确定了RNA结合蛋白CPEB 3在抑制细胞增殖和迁移中的新作用以及结直肠癌细胞中的潜在机制。
As RNA-binding proteins, cytoplasmic polyadenylation element binding proteins (CPEBs) have drawn increasing attention for their function of controlling gene expression related to malignant transformation via post-transcriptional regulation. However, the contribution of CPEB3 to malignant development in cancers is poorly understood. In this study, we explored the clinical, biological, and mechanical role of CPEB3 in colorectal cancer progression. We showed that colorectal cancer tissues exhibited dampened CPEB3 expression which was closely associated with poor prognosis in patients with colorectal cancer (47 vs. 62 months, P = 0.035, n=99). Down-regulation CPEB3 promoted proliferation, migration, and invasion in colorectal cancer cells and vice versa. Mechanistically, CPEB3 performed as an RNA binding protein binding to 3ʹUTR of JAK1 mRNA to inhibit JAK/STAT pathways in colorectal cancer cells. Knockdown of CPEB3 induced active JAK-STAT signaling, thereby triggering the proliferation and metastasis capacity of colorectal cancer cells. These results suggest that CPEB3 functions as a tumor suppressor in colorectal cancer through its post-transcriptional regulation of JAK/STAT signaling. Implications: This study identified a novel role of the RNA binding protein CPEB3 in inhibiting cell proliferation and migration as well as the underlining mechanisms in colorectal cancer cells.
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DOI：
10.1016/j.bbrc.2019.02.006
发表时间：
2019-04-02
影响因子：
3.1
作者：
Lin, Hao;Guo, Qingqing;Wen, Jianbo
通讯作者：
Wen, Jianbo
影响因子：
11.4
作者：
Huang, Yi-Shuian;Kan, Ming-Chung;Richter, Joel D.
通讯作者：
Richter, Joel D.
影响因子：
7.3
作者：
Phesse, Toby J.;Buchert, Michael;Ernst, Matthias
通讯作者：
Ernst, Matthias
肥胖症和慢性全身性炎症对转移性结直肠癌患者的关节预后作用。
影响因子：
6.2
作者：
Shah MS;Fogelman DR;Raghav KP;Heymach JV;Tran HT;Jiang ZQ;Kopetz S;Daniel CR
通讯作者：
Daniel CR
影响因子：
64.8
作者：
通讯作者：
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