OncoTargets and Therapy (Apr 2019)
Whole transcriptome sequencing identifies crucial genes associated with colon cancer and elucidation of their possible mechanisms of action
Abstract
Yang Yang, Yanan Zhao, Wenlong Zhang, Yuansong Bai Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China Purpose: This study aimed to investigate the key long non-coding RNAs (lncRNAs) associated with colon cancer and elucidate their possible mechanisms of action.Patients and methods: Eight early-stage (ES) colon tumor tissues, eight late-stage (LS) colon tumor tissues, and eight normal tissues were collected, and they were subjected to high-throughput RNA sequencing. Subsequently, comprehensive bioinformatics analyses, including the identification of differentially expressed mRNAs and lncRNAs, functional enrichment analysis, and construction of a protein–protein interaction network and an miRNA–lncRNA–mRNA regulatory network were performed. Additionally, the expression of key lncRNAs was verified using real-time quantitative PCR (qPCR).Results: In total, 549 common differentially expressed mRNAs and 30 common differentially expressed lncRNAs were identified in both the ES and LS colon cancer samples upon comparison with the normal samples. Functional enrichment analysis showed that KIAA0125 was significantly enriched in the PI3K-Akt signaling pathway and that MSTRG.35002.1 was markedly enriched in BMP signaling-related functions. Moreover, key miRNA–lncRNA–mRNA relationships, such as hsa-miR-29b-3p-KIAA0125-BCL2 and hsa-miR-29b-3p-MSTRG.35002.1-MMP2, were identified. Notably, the qPCR assay confirmed that KIAA0125 and MSTRG.35002.1 were significantly downregulated in both ES and LS colon tumor tissues compared with normal colon tissues.Conclusion: Our findings indicate that key lncRNAs, including KIAA0125 and MSTRG.35002.1, may be involved in colorectal cancer (CRC) development. Downregulation of KIAA0125 may contribute to CRC development via sponging of hsa-miR-29b-3p to regulate BCL2 expression or regulating the PI3K-Akt signaling pathway. Downregulation of MSTRG.35002.1 may promote CRC development via sponging of hsa-miR-29b-3p to regulate MMP2 expression or regulating the BMP signaling pathway. Keywords: colon cancer, differentially expressed mRNAs, differentially expressed lncRNAs, molecular mechanism, CeRNA network
