Song Kai, Liu Chao, Zhang Jiashuai, Yao Yang, Xiao Huiting, Yuan Rongqiang, Li Keru, Yang Jia, Zhao Wenyuan, Zhang Yanqiao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, Guangdong, 519000, China.
Heliyon. 2022 Mar 5;8(3):e09068. doi: 10.1016/j.heliyon.2022.e09068. eCollection 2022 Mar.
Single-driver molecular events specific to the metabolic colorectal cancer (CRC) have not been clearly elucidated. Herein, we identified 12 functional miRNAs linked to activated metabolism by integrating multi-omics features in metabolic CRC. These miRNAs exhibited significantly enriched CRC driver miRNAs, significant impacts on CRC cell growth and significantly correlated metabolites. Importantly, miR-20a is minimally expressed in normal colorectal tissues but highly expressed in metabolic CRC, suggesting the potential therapeutic target. Bioinformatics analyses further revealed miR-20a as the most powerful determinant that regulates a cascade of dysregulated events, including Wnt signaling pathway, core enzymes involved in FA metabolism program and triacylglycerol abundances. In vitro assays demonstrated that elevated miR-20a up-regulated FA synthesis enzymes via Wnt/β-catenin signaling, and finally promoted proliferative and migration of metabolic CRC cells. Overall, our study revealed that miR-20a promoted progression of metabolic CRC by regulating FA metabolism and served as a potential target for preventing tumor metastasis.
代谢性结直肠癌（CRC）特有的单驱动分子事件尚未得到明确阐释。在此，我们通过整合代谢性CRC中的多组学特征，鉴定出12种与激活代谢相关的功能性miRNA。这些miRNA表现出显著富集的CRC驱动miRNA，对CRC细胞生长有显著影响，且与代谢产物显著相关。重要的是，miR-20a在正常结直肠组织中表达极低，但在代谢性CRC中高表达，提示其具有潜在的治疗靶点。生物信息学分析进一步揭示，miR-20a是调节一系列失调事件的最有力决定因素，这些事件包括Wnt信号通路以及参与脂肪酸代谢程序的核心酶和三酰甘油丰度。体外实验表明，miR-20a的升高通过Wnt/β-连环蛋白信号上调脂肪酸合成酶，最终促进代谢性CRC细胞的增殖和迁移。总体而言，我们的研究表明，miR-20a通过调节脂肪酸代谢促进代谢性CRC的进展，并作为预防肿瘤转移的潜在靶点。
