Abstract
BackgroundLong noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers development. However, the expression pattern and biological function of SPRY4-IT1 in gastric cancer is still not well documented. Hence, we carried out the present study to investigate the potential role of SPRY4-IT1 in gastric carcinogenesis.MethodsQRT-PCR was performed to detect the expression of SPRY4-IT1 in 61 pairs of gastric cancer samples. Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of SPRY4-IT1. The effect of SPRY4-IT1 on proliferation was evaluated by MTT and colony formation assays. Gastric cancer cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice to study the effect of SPRY4-IT1 on tumorigenesis and metastasis in vivo. Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry. ChIP assays were performed to investigate the effect of DNMT1 on SPRY4-IT1 expression. Differences between groups were tested for significance using Student’s t test (two-tailed).ResultsSPRY4-IT1 expression is decreased in gastric cancer tissues and associated with larger tumor size, advanced pathological stage, deeper depth of invasion and lymphatic metastasis. Patients with lower SPRY4-IT1 expression had a relatively poor prognosis. DNA methylation may be a key factor in controlling the SPRY4-IT1 expression. Furthermore, SPRY4-IT1 contributed to gastric cancer cells metastasis might partly via regulating epithelial–mesenchymal transition (EMT) process.ConclusionLow expression of SPRY4-IT1 is involved in progression and metastasis of gastric cancer and may represent a novel biomarker of poor prognosis in patients with gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0595-9) contains supplementary material, which is available to authorized users.
Highlights
Long noncoding RNAs are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis
The SPRY4-IT1 level was significantly down-regulated in gastric cancer tissue compared with corresponding adjacent non-tumor tissues. (P = 0.001, Wilcoxon test). These data indicate that SPRY4-IT1 expression may be related to gastric cancer pathogenesis
In summary, we demonstrated that the decreased SPRY4-IT1 expression is a common event underlying the progression and metastasis of gastric cancer, indicating that SPRY4-IT1 may be an indicator of poor survival rate and a negative prognostic factor for gastric cancer patients
Summary
Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. Xie et al J Transl Med (2015) 13:250 gastric cancer related lncRNAs and investigate their roles in gastric carcinogenesis. LncRNAs are less well characterized compared with microRNAs, increasing evidence suggest that lncRNAs could play critical roles in regulation of diverse cellular processes such as stem cell pluripotency, cell differentiation, cell growth, cell apoptosis and cancer metastasis [7,8,9,10,11,12,13]. LncRNAs may function as cis- or trans-regulators of gene expression via playing as scaffolds for chromatin modifying complexes, decoys to transcription factors or serving as ‘sponge’ to microRNAs [14,15,16,17]
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