Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
Kai Song,
Chao Liu,
Jiashuai Zhang,
Yang Yao,
Huiting Xiao,
Rongqiang Yuan,
Keru Li,
Jia Yang,
Wenyuan Zhao,
Yanqiao Zhang
Affiliations
Kai Song
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
Chao Liu
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150086, China
Jiashuai Zhang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China
Yang Yao
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150086, China
Huiting Xiao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China
Rongqiang Yuan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China
Keru Li
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China
Jia Yang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China
Wenyuan Zhao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China; Corresponding author.
Yanqiao Zhang
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150086, China; Corresponding author.
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.
