Wu Jialin, Chen Zehong, Liu Wenwei, Zhang Yongxin, Feng Wei, Yuan Yujie, Ye Jinning, Wang Liang, Cai Shirong, He Yulong, Wu Suijing, Song Wu
Center of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, P.R. China.
Department of Hepatobiliary and Pancreatic Surgery, Union Shenzhen Hospital Huazhong University of Science and Technology, Shenzhen, Guangdong Province, P.R. China.
Oncol Res. 2020 Nov 23. doi: 10.3727/096504020X16061317886881.
MicroRNA-188-5p (miR-188) enhances oncologic progression in various human malignancies. This study aimed to explore its role in colorectal cancer (CRC). Human CRC tissues paired with normal tissues, and several CRC cell lines were utilized. Real-time quantitative PCR was applied to measure the expression of miR-188. Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function. The proliferation, migration and invasion of cancer cells were evaluated by CCK8, wound-healing and transwell assays, respectively. Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays. Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues, as well as in various CRC cell lines. High expression of miR-188 was strongly associated with advanced tumor stage, accompanied with significant tumor cell proliferation, invasion and migration. It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation. All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.
微小RNA-188-5p（miR-188）促进多种人类恶性肿瘤的肿瘤进展。本研究旨在探讨其在结直肠癌（CRC）中的作用。使用了与正常组织配对的人类CRC组织以及几种CRC细胞系。应用实时定量PCR检测miR-188的表达。采用过表达和敲低技术来研究miR-188的功能，并探究FOXL1/Wnt信号通路是否介导该功能。分别通过CCK8、伤口愈合和Transwell实验评估癌细胞的增殖、迁移和侵袭能力。通过双荧光素酶报告基因实验验证FOXL1是否为miR-188的直接靶点。与配对的正常组织相比，CRC组织以及各种CRC细胞系中miR-188的水平均上调。miR-188的高表达与肿瘤晚期密切相关，同时伴有明显的肿瘤细胞增殖、侵袭和迁移。证实FOXL1在miR-188调控与下游Wnt/β-连环蛋白信号激活之间发挥正向串扰作用。所有研究结果表明，miR-188通过靶向FOXL1/Wnt信号通路促进CRC细胞增殖和侵袭，未来可能成为人类CRC的潜在治疗靶点。
