Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer

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...

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Main Authors: Kai Song, Chao Liu, Jiashuai Zhang, Yang Yao, Huiting Xiao, Rongqiang Yuan, Keru Li, Jia Yang, Wenyuan Zhao, Yanqiao Zhang
Format: Article
Language:English
Published: Elsevier 2022-03-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022003565
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author Kai Song
Chao Liu
Jiashuai Zhang
Yang Yao
Huiting Xiao
Rongqiang Yuan
Keru Li
Jia Yang
Wenyuan Zhao
Yanqiao Zhang
author_facet Kai Song
Chao Liu
Jiashuai Zhang
Yang Yao
Huiting Xiao
Rongqiang Yuan
Keru Li
Jia Yang
Wenyuan Zhao
Yanqiao Zhang
author_sort Kai Song
collection DOAJ
description 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.
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spelling doaj.art-d1a3a9167af5400f8c624f8643c168162022-12-21T18:13:35ZengElsevierHeliyon2405-84402022-03-0183e09068Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancerKai Song0Chao Liu1Jiashuai Zhang2Yang Yao3Huiting Xiao4Rongqiang Yuan5Keru Li6Jia Yang7Wenyuan Zhao8Yanqiao Zhang9College 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, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150086, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150086, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405844022003565miRNAConsensus molecular subtypeFatty acid metabolismWnt signaling pathwayMetabolic colorectal cancer
spellingShingle Kai Song
Chao Liu
Jiashuai Zhang
Yang Yao
Huiting Xiao
Rongqiang Yuan
Keru Li
Jia Yang
Wenyuan Zhao
Yanqiao Zhang
Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
Heliyon
miRNA
Consensus molecular subtype
Fatty acid metabolism
Wnt signaling pathway
Metabolic colorectal cancer
title Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
title_full Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
title_fullStr Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
title_full_unstemmed Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
title_short Integrated multi-omics analysis reveals miR-20a as a regulator for metabolic colorectal cancer
title_sort integrated multi omics analysis reveals mir 20a as a regulator for metabolic colorectal cancer
topic miRNA
Consensus molecular subtype
Fatty acid metabolism
Wnt signaling pathway
Metabolic colorectal cancer
url http://www.sciencedirect.com/science/article/pii/S2405844022003565
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