Department of GI Medicine, Linyi Central Hospital, Linyi, China.
Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10535-10541. doi: 10.26355/eurrev_202010_23406.
This study aims to illustrate the role of microRNA-548 (miR-548) in regulating the development of colorectal cancer (CRC) and the involvement of WNT2.
MiR-548b levels in CRC species and paracancerous ones were detected. The relationship between miR-548b level and clinical parameters of CRC patients was analyzed. After overexpression of miR-548b, the changes in the proliferative and apoptotic capacities of Sw620 and HT29 cells were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, and flow cytometry, respectively. At last, the involvement of WNT2, the downstream gene of miR-548b, was detected by Luciferase assay and rescue experiments.
Results manifested that miR-548b was lowly expressed in CRC species than paracancerous ones, and in vitro level of miR-548b was downregulated in CRC cell lines as well. Compared with CRC patients in T1-T2, miR-548b level was lower in T3-T4 CRC. Moreover, CRC patients with lymphatic metastasis had lower level of miR-548b than those without. Overexpression of miR-548b suppressed proliferative capacity and induced apoptosis in CRC cells. Besides, it was found that WNT2 was the downstream gene of miR-548b, and its level was negatively regulated by miR-548b in CRC. Furthermore, rescue experiments showed that WNT2 was responsible for CRC development regulated by miR-548b.
MiR-548b is closely linked to tumor stage and lymphatic metastasis of CRC, and it alleviates the malignant development of CRC by targeting WNT2.
本研究旨在阐明 microRNA-548（miR-548）在调控结直肠癌（CRC）发展中的作用及 WNT2 的参与情况。
检测 CRC 组织和癌旁组织中 miR-548b 的水平。分析 miR-548b 水平与 CRC 患者临床参数的关系。过表达 miR-548b 后，通过细胞计数试剂盒-8（CCK-8）、集落形成实验和流式细胞术分别评估 Sw620 和 HT29 细胞增殖和凋亡能力的变化。最后，通过荧光素酶报告基因和挽救实验检测 WNT2（miR-548b 的下游基因）的参与情况。
结果表明，miR-548b 在 CRC 组织中的表达低于癌旁组织，CRC 细胞系中也存在 miR-548b 水平下调。与 T1-T2 期 CRC 患者相比，T3-T4 期 CRC 患者 miR-548b 水平较低。此外，有淋巴转移的 CRC 患者 miR-548b 水平低于无淋巴转移的患者。过表达 miR-548b 抑制 CRC 细胞的增殖能力并诱导其凋亡。此外，发现 WNT2 是 miR-548b 的下游基因，其在 CRC 中受 miR-548b 的负调控。此外，挽救实验表明，WNT2 负责 miR-548b 调节的 CRC 发展。
miR-548b 与 CRC 的肿瘤分期和淋巴转移密切相关，通过靶向 WNT2 减轻 CRC 的恶性发展。
