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. 2018 Apr;17(4):5666-5675.
doi: 10.3892/mmr.2018.8576. Epub 2018 Feb 8.

Differential expression profiles of long noncoding RNA and mRNA in colorectal cancer tissues from patients with lung metastasis

Ruo Shu #  1 , Yu Xu #  1 , Yan Tian  2 , Yujian Zeng  1 , Liang Sun  2 , Fangyou Gong  2 , Yi Lei  2 , Kunhua Wang  1 , Huayou Luo  1
Affiliations

Differential expression profiles of long noncoding RNA and mRNA in colorectal cancer tissues from patients with lung metastasis

Ruo Shu et al. Mol Med Rep. 2018 Apr.

Abstract

Lungs are the most common extra‑abdominal site of metastasis of colorectal cancer (CRC), in which long noncoding RNA (lncRNA) may serve a role. In the present study, a high‑throughput microarray assay was performed to detect lncRNA expression and identify novel targets for further study of lung metastasis in CRC. In the CRC tissues from patients with lung metastasis, 7,632 lncRNA (3,574 upregulated and 4,058 downregulated) and 6,185 mRNA (3,394 upregulated and 2,791 downregulated) were detected to be differentially expressed with a fold change ≥2 and P<0.05 compared with the CRC tissues without metastasis. A total of six differentially regulated lncRNA were confirmed by reverse transcription‑quantitative polymerase chain reaction in 20 pairs of CRC samples. Furthermore, gene ontology and pathway analysis were conducted to predict the possible roles of the identified mRNA. The upregulated mRNA were associated with cell division (biological processes), protein kinase B binding (molecular functions) and cellular components. The downregulated mRNA were associated with cell adhesion, platelet‑derived growth factor binding and membrane components. Pathway analysis determined that the upregulated mRNA were associated with the Wnt signaling pathway in the CRC tissues from patients with lung metastasis, while the downregulated mRNA were associated with the phosphoinositide 3‑kinase/Akt signaling pathway. The results of the present study suggested that differentially expressed lncRNA may be associated with lung metastasis and may provide insights into the biology and prevention of lung metastasis.

Keywords: colorectal cancer; lung metastasis; long noncoding RNA; biological process; molecular function; cellular component.

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Figures

Figure 1.
Figure 1.
Differentially expressed lncRNA between patients with colorectal cancer with (Exp) or without (Ctrl) lung metastasis. (A) Heat map of upregulated lncRNA. (B) Heat map of downregulated lncRNA. Each column represents one sample. lncRNA, long noncoding RNA; Exp, experimental group; Ctrl, control.
Figure 2.
Figure 2.
Differentially expressed mRNA between patients with colorectal cancer with (Exp) or without (Ctrl) lung metastasis. (A) Heat map of upregulated mRNA. (B) Heap map of downregulated mRNA. Each column represents one sample. Exp, experimental group; Ctrl, control.
Figure 3.
Figure 3.
Validation of the microarray assay of differentially expressed lncRNA using RT-qPCR. (A) Comparative expression of lncRNA between the Exp (CRC with lung metastasis) and the Ctrl (CRC without lung metastasis) group. The data are presented as the mean + standard deviation. **P<0.05 as indicated. (B) Comparison of the results obtained by microarray with the results obtained by RT-qPCR. RT-qPCR, reverse transcription-quantitative polymerase chain reaction; CRC, colorectal cancer; lncRNA, long noncoding RNA; Exp, experimental; Ctrl, control; HOTTIP, HOXA distal transcript antisense RNA; UCA1, urothelial cancer associated 1; MALAT1, metastasis associated lung adenocarcinoma transcript 1; MEG3, maternally expressed 3.
Figure 4.
Figure 4.
Analysis of upregulated mRNA involved in BPs. (A) BP classification based on the number of DE mRNA. (B) The most represented BPs based on the enrichment score. (C) The most represented BPs according to the fold enrichment. BP, biological process; CENP-A, centromere protein A; GO, gene ontology; DE, differentially expressed; Sig, significant.
Figure 5.
Figure 5.
Analysis of downregulated mRNA involved in BPs. (A) BP classification based on the number of DE mRNA. (B) The most represented BPs based on the enrichment score. (C) The most represented BPs according to the fold enrichment. BP, biological process; GO, gene ontology; DE, differentially expressed; Sig, significant.
Figure 6.
Figure 6.
Analysis of upregulated mRNA involved in MFs. (A) MF classification based on the number of DE mRNA. (B) The most represented MFs based on the enrichment score. (C) The most represented MFs according to the fold enrichment. MF, molecular function; GO, gene ontology; DE, differentially expressed; Sig, significant.
Figure 7.
Figure 7.
Analysis of downregulated mRNA involved in MFs. (A) MF classification based on the number of DE mRNA. (B) The most represented MFs based on the enrichment score. (C) The most represented MFs according to the fold enrichment. MF, molecular function; GO, gene ontology; DE, differentially expressed; Sig, significant.
Figure 8.
Figure 8.
Analysis of upregulated mRNA involved in CCs. (A) CC classification based on the number of DE mRNA. (B) The most represented CCs based on the enrichment score. (C) The most represented CCs according to the fold enrichment. CC, cellular component; GO, gene ontology; DE, differentially expressed; Sig, significant.
Figure 9.
Figure 9.
Analysis of downregulated mRNA involved in CCs. (A) CC classification based on the number of differentially expressed mRNA. (B) The most represented CCs based on the enrichment score. (C) The most represented CCs according to the fold enrichment. CC, cellular component; GO, gene ontology; DE, differentially expressed; Sig, significant.
Figure 10.
Figure 10.
Kyoto Encyclopedia of Genes and Genomes pathway analysis of DE mRNA. The top 10 pathways enriched by (A) upregulated and (B) downregulated mRNA. DE, differentially expressed; Sig, significant; PPAR, peroxisome proliferator-activated receptor; ECM, extracellular matrix; PI3K, phosphoinositide 3-kinase.
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