Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Aging (Albany NY). 2021 Mar 3;13(5):7608-7626. doi: 10.18632/aging.202657.
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).
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 and . Furthermore, bioinformatics analysis, dual-luciferase reporter assay, chromatin immunecipitation assay, western blotting and recovery experiments were implemented to investigate the underlying molecular mechanism.
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.
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.
miR-452-5p 在多种肿瘤的发展中起着至关重要的作用，但关于其在结直肠癌（CRC）中的生物学功能和机制知之甚少。
通过实时定量 PCR（qRT-PCR）检测 CRC 组织和细胞中 miR-452-5p 的表达水平。此外，通过功能实验和进一步的生物信息学分析、双荧光素酶报告基因检测、染色质免疫沉淀实验、Western blot 及恢复实验研究 miR-452-5p 对 CRC 的生物学影响及其潜在的分子机制。
miR-452-5p 在 CRC 组织中呈上调表达。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，进而激活 ERK/MAPK 信号通路，其转录受 c-Jun 调控。
综上所述，miR-452-5p 在 CRC 中呈上调表达，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。
