MiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop.
MiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop.
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DOI：
10.18632/aging.202657
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发表时间：
2021-03-03
期刊：
影响因子：
--
通讯作者：
Li A
中科院分区：
文献类型：
--
作者：
Lin X;Han L;Gu C;Lai Y;Lai Q;Li Q;He C;Meng Y;Pan L;Liu S;Li A
背景：MiR-452-5p在多种肿瘤的发生发展中发挥重要作用，但其在结直肠癌（CRC）中的生物学功能和机制知之甚少。方法：采用实时定量PCR（qRT-PCR）检测CRC组织和细胞中miR-452-5p的表达水平。此外，通过体外和体内功能实验研究了miR-452-5p对CRC的生物学效应。此外，还进行了生物信息学分析、双荧光素酶报告基因测定、染色质免疫沉淀测定、蛋白质印迹和恢复实验来研究潜在的分子机制。结果：CRC组织中miR-452-5p的表达水平上调。 MiR-452-5p促进CRC细胞增殖、细胞周期转变和化疗耐药，并抑制细胞凋亡。此外，miR-452-5p直接靶向PKN2和DUSP6，随后激活ERK/MAPK信号通路，并受到c-Jun的转录调控。结论：综上所述，miR-452-5p在CRC中表达上调，通过激活miR-452-5p—PKN2/DUSP6—c-Jun正反馈环促进CRC的进展。这些发现表明 miR-452-5p 可能作为 CRC 的潜在治疗靶点和临床反应生物标志物。
Background: MiR-452-5p plays an essential role in the development of a variety of tumors, but little is known about its biological function and mechanism in colorectal cancer (CRC). Methods: The expression levels of miR-452-5p in CRC tissues and cells were detected by real-time quantitative PCR (qRT-PCR). Besides, the biological effects of miR-452-5p on CRC were investigated by functional experiments in vitro and in vivo. Furthermore, bioinformatics analysis, dual-luciferase reporter assay, chromatin immunecipitation assay, western blotting and recovery experiments were implemented to investigate the underlying molecular mechanism. Results: The expression level of miR-452-5p was up-regulated in CRC tissues. MiR-452-5p promoted CRC cell proliferation, cell cycle transition and chemoresistance, and inhibited cell apoptosis. Moreover, miR-452-5p directly targeted PKN2 and DUSP6 and subsequently activated the ERK/MAPK signaling pathway, and it was transcriptionally regulated by c-Jun. Conclusion: To conclude, miR-452-5p expression is up-regulated in CRC, which promotes the progression of CRC by activating the miR-452-5p—PKN2/DUSP6—c-Jun positive feedback loop. These findings indicate that miR-452-5p may act as a potential therapeutic target and clinical response biomarker for CRC.
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结肠癌细胞中的PKN2通过调节DUSP6-Erk1/2通路抑制肿瘤相关巨噬细胞的M2表型极化
影响因子：
37.3
作者：
Cheng Y;Zhu Y;Xu J;Yang M;Chen P;Xu W;Zhao J;Geng L;Gong S
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