Abstract
BackgroundLong noncoding RNAs (lncRNAs) play important roles in carcinogenesis. However, the roles of metabolism‐associated lncRNAs in cancers are still unclear.MethodsA microarray of metabolism‐associated lncRNAs was used to detect their expression patterns between gastric cancer and paired nontumorous tissues. Its results and gastric cancer differential gene expression data from public databases were used to screen the metabolic pathway‐associated lncRNAs. A metabolic network with microRNAs (miRNAs), lncRNAs, and protein‐coding genes was further constructed. Finally, the expression of TOPORS antisense RNA 1 (TOPORS‐AS1), a screened highly expressed lncRNA and its associated protein‐coding gene, NADH: ubiquinone oxidoreductase subunit B6 (NDUFB6), were verified by reverse transcription polymerase chain reaction.ResultsA total of eight upregulated and one downregulated lncRNAs and 25 upregulated and 20 downregulated protein‐coding genes were found to be involved in metabolism in gastric cancer. Within the lncRNAs–miRNAs–mRNAs metabolic network, 78 miRNA‐target links, 546 positive coexpression relationships, and 191 protein–protein interactions were found. The expression of TOPORS‐AS1 and its associated gene, NDUFB6 in gastric cancer tissues was significantly lower than that in adjacent nontumor tissues. Moreover, NDUFB6 expression was associated with the invasion and distal metastasis of gastric cancer.ConclusionsThe metabolism‐associated lncRNAs play important roles in the occurrence of gastric cancer.
Highlights
Long noncoding RNAs play important roles in carcinogenesis
Several studies have showed that the expression of glucose transporter‐1 (GLUT‐1), which is involved in the glycolytic pathway, is significantly correlated with prognosis of gastric carcinoma (Kawamura et al, 2001; Noguchi et al, 1999)
The LncPathTM human metabolism pathway Long noncoding RNAs (lncRNAs) microarray (Arraystar, Rockville, MD, USA) was used, which contains probes for both lncRNAs and mRNAs to simultaneously profile the expression of 965 lncRNAs and 458 protein‐ coding gene targets related to the metabolic signaling pathway
Summary
One of the most common cancers worldwide, is a major public health problem (Wang et al, 2018). A hallmark of cancers, contributes to cancers from initiation, growth, and maintenance to malignant transformation (Hanahan & Weinberg, 2011). Identifying these metabolic alterations and the underlying regulatory mechanisms in cancers could open a window of opportunity for therapeutic intervention. Most cancer cells prefer to produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid cycle, even under aerobic conditions (Warburg effect) (Hanahan & Weinberg, 2011). Metastasis‐associated in colon cancer‐1 (MACC1), a long noncoding RNA (lncRNA), contributes to the Warburg effect by upregulating the expression and activities of a series of glycolytic enzymes in gastric cancer cells, including hexokinase, pyruvate dehydrogenase kinase, and lactate dehydrogenase (Lin et al, 2015). The typical lncRNA and its associated metabolic gene were confirmed by experiments in gastric cancer tissues
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