Temporal expression and functional analysis of long non‐coding RNAs in colorectal cancer initiation

Abstract

Long non‐coding RNAs (lncRNAs) have potential applications in clinical diagnosis and targeted cancer therapies. However, the expression profile of lncRNAs in colorectal cancer (CRC) initiation is still unclear. In this study, the expression profiles of lncRNAs and mRNAs were determined by microarray at specific tumour stages in an AOM/DSS‐induced primary colon cancer model. The temporal expression of lncRNAs was analysed by K‐means clustering. Additionally, weighted correlation network analysis (WGCNA) and gene ontology analysis were performed to construct co‐expression networks and establish functions of the identified lncRNAs and mRNAs. Our results suggested that 4307 lncRNAs and 5798 mRNAs are deregulated during CRC initiation. These differential expression genes (DEGs) exhibited a clear correlation with the differential stage of tumour initiation. WGCNA results suggested that a series of hub lncRNAs are involved in regulating cell stemness, colon inflammation, oxidative stress response and cell death at each stage. Among them, lncRNA H19 was up‐regulated in colon tumours and correlated with poor patient prognosis. Collectively, we have been the first to demonstrate the temporal expression and function of lncRNAs in CRC initiation. These results provide novel diagnosis and therapy targets for CRC.

Insulin-Like Growth Factor 2 (IGF2) Signaling in Colorectal Cancer—From Basic Research to Potential Clinical Applications

“…The clinical significance (diagnostic-prognostic response to therapy) of numerous miRNAs in CRCs is also confirmed by meta-analyses [44,45]. The recent data of Dai et al (2019) suggests that 4307 lncRNAs and 5798 mRNAs are deregulated during CRC initiation [46].…”

SEZ6L2 knockdown impairs tumour growth by promoting caspase‐dependent apoptosis in colorectal cancer

“…Suppression of the activator protein 1 (AP‐1), regulated by IFN (SARI), was demonstrated to be down‐regulated in CRC, and SARI expression was inversely correlated with poor clinical outcomes in patients with CRC . Furthermore, deregulated long non‐coding RNAs were also involved in regulating cell stemness, colon inflammation, oxidative stress response and cell death during CRC initiation and progression . SEZ6L2 expression in mouse embryos was restricted to the spinal cord and brain, while in the human foetal brain, it was highest in the post‐mitotic cortical layers, hippocampus, amygdala, and thalamus .…”

lncRNA‑ATB promotes stemness maintenance in colorectal cancer by regulating transcriptional activity of the β‑catenin pathway

“…lncRNAs exert their biological functions by binding to DNA, RNA and proteins, thereby regulating protein expression at the transcriptional or post-transcriptional level (9,10). Numerous lncRNAs are dysregulated in different types of cancer and are correlated with tumor cell proliferation, apoptosis, migration and stem-like properties (11)(12)(13). lncRNA activated by transforming growth factor-β (ATB) has been identified as a novel transforming growth factor-β (TGF-β)-induced lncRNA that stimulates cancer cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) and angiogenesis in lung, bladder, breast and gastric cancer (14)(15)(16)(17).…”