Altered expression profiles of circular RNA in colorectal cancer tissues from patients with lung metastasis

Abstract

The lung is the most common extra-abdominal site of metastasis in colorectal cancer (CRC), in which circular RNA (circRNA) may have a crucial role. Therefore, the present study detected circRNA expression to identify novel targets to further study lung metastasis in CRC. In the present study, total RNA was extracted from CRC tissues of patients with and without lung metastasis to perform high-throughput microarray assay in order to detect differentially expressed circRNA. Following this, gene ontology (GO) and pathway analyses of the genes producing differentially expressed circRNA were performed to predict the function of circRNA using standard enrichment computational methods. Additionally, the circRNA/microRNA (miRNA) interactions were constructed with bioinformatics methods to predict the binding of miRNA with circRNA. In the CRC tissues from patients with lung metastasis, 431 circRNA were detected to be differentially expressed, including 192 upregulated and 239 downregulated over 2-fold compared with the CRC tissues without metastasis. Furthermore, GO analysis revealed that the genes producing upregulated circRNA were involved in DNA repair, while the genes producing downregulated circRNA were enriched in signal transduction. By pathway analysis, it was identified that the genes producing downregulated circRNA were involved in the nuclear factor-κB and Wnt signaling pathway in the CRC tissues from patients with lung metastasis compared with the CRC tissues without metastasis. In addition, it was demonstrated that hsa_circRNA_105055, hsa_circRNA_086376 and hsa_circRNA_102761 could commonly bind with miR-7 regulating target genes PRKCB, EPHA3, BRCA1 and ABCC1. The findings of the present study may provide a novel perspective on circRNA and lay a foundation for future research of potential roles of circRNA in CRC with lung metastasis.

Emerging roles of circRNA in formation and progression of cancer

“…When comparing two groups of profile differences, the fold change (i.e. the ratio of the group averages) between the groups for each circRNA is computed [28] .…”

“…GO analysis (geneontology.org) can be used to construct meaningful annotation of gene products. GO contains three domains, including biological process (BP), cellular components (CC) and molecular function (MF) [28] . The Gene Ontology, which provides the logical structure of the biological functions ('terms') and their relationships to one another, manifested as a directed acyclic graph the corpus of GO annotations, evidence-based statements relating a specific gene product (a protein, non-coding RNA, or macromolecular complex, which we often refer to as 'genes' for simplicity) to a specific ontology term.…”

“…KEGG is utilized to harvest pathway clusters covering the knowledge of the molecular interaction and reaction networks in genes producing differentially expressed circRNA [28] . The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle.…”

“…Hsa_circ_0126897_CBC1 is thought to be a potential biomarker for CRC, and the cell cycle is closely associated with the occurrence and development of CRC using CapitalBio microarray technology [58] . According to the study, 431 circRNAs are found differentially expressed in CRC tissues from patients with pulmonary metastasis compared with tissues without metastasis [28] . Another study revealed that hsa_circRNA_105055 (upregulated), hsa_circRNA_086376 (downregulated) or hsa_circRNA_102761 (downregulated) may regulate the pulmonary metastasis of CRC through binding with miR-7 to regulate protein kinase C beta (PRKCB) that is involved in the NF-κB or Wnt signaling pathway [28] (Table 3).…”

“…According to the study, 431 circRNAs are found differentially expressed in CRC tissues from patients with pulmonary metastasis compared with tissues without metastasis [28] . Another study revealed that hsa_circRNA_105055 (upregulated), hsa_circRNA_086376 (downregulated) or hsa_circRNA_102761 (downregulated) may regulate the pulmonary metastasis of CRC through binding with miR-7 to regulate protein kinase C beta (PRKCB) that is involved in the NF-κB or Wnt signaling pathway [28] (Table 3). Circ-BANP down --PI3 K/Akt [29] CircHIPK3 up miR-7 c-Myb [30] Hsa_circ_0000069 up ---- [55] Hsa_circ_001988 down ---- [56] Hsa_circ_007534 up ---- [57] CircITGA7 down miR-370-3p Ras [79] Circ_0026344 down miR-21,miR-31 -- [80]…”