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Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition.

Xie M, Nie FQ, Sun M, Xia R, Liu YW, Zhou P, De W, Liu XH - J Transl Med (2015)

Bottom Line: Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry.Differences between groups were tested for significance using Student's t test (two-tailed).Patients with lower SPRY4-IT1 expression had a relatively poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. 1115769204@qq.com.

ABSTRACT

Background: Long 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.

Methods: QRT-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).

Results: SPRY4-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.

Conclusion: Low 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.

No MeSH data available.


Related in: MedlinePlus

Relative SPRY4-IT1 expression and its clinical significance in gastric cancer tissues. a SPRY4-IT1 expression in matched cancerous tissues and adjacent noncancerous tissues from 61 gastric cancer patients were measured by qRT-PCR. Relative gene expression determinations were made with the comparative delta CT normalized to GAPDH expression (P = 0.001). b According to the median ratio of relative SPRY4-IT1 expression (0.535) in tumor tissues, SPRY4-IT1 expression was classified into two groups: relative high-SPRY4-IT1 group (n = 30, red column) and relative low- SPRY4-IT1 group (n = 31, blue column). Data was presented as fold-change in tumor tissues relative to normal tissues (P = 0.001). c, d Kaplan–Meier overall survival and disease-free survival curves according to SPRY4-IT1 expression level. Patients with decreased SPRY4-IT1 expression (n = 31) showed reduced survival times compared with patients with high level of SPRY4-IT1 expression (n = 31) (P = 0.001 or 0.002, log-rank test).
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Fig1: Relative SPRY4-IT1 expression and its clinical significance in gastric cancer tissues. a SPRY4-IT1 expression in matched cancerous tissues and adjacent noncancerous tissues from 61 gastric cancer patients were measured by qRT-PCR. Relative gene expression determinations were made with the comparative delta CT normalized to GAPDH expression (P = 0.001). b According to the median ratio of relative SPRY4-IT1 expression (0.535) in tumor tissues, SPRY4-IT1 expression was classified into two groups: relative high-SPRY4-IT1 group (n = 30, red column) and relative low- SPRY4-IT1 group (n = 31, blue column). Data was presented as fold-change in tumor tissues relative to normal tissues (P = 0.001). c, d Kaplan–Meier overall survival and disease-free survival curves according to SPRY4-IT1 expression level. Patients with decreased SPRY4-IT1 expression (n = 31) showed reduced survival times compared with patients with high level of SPRY4-IT1 expression (n = 31) (P = 0.001 or 0.002, log-rank test).

Mentions: We firstly examined SPRY4-IT1 expression level in 61 paired gastric cancer samples and adjacent normal tissues using qRT-PCR approach, and gene expression was calculated relative to that of an internal control (ΔCt). As shown in Fig. 1a, 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.Fig. 1


Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition.

Xie M, Nie FQ, Sun M, Xia R, Liu YW, Zhou P, De W, Liu XH - J Transl Med (2015)

Relative SPRY4-IT1 expression and its clinical significance in gastric cancer tissues. a SPRY4-IT1 expression in matched cancerous tissues and adjacent noncancerous tissues from 61 gastric cancer patients were measured by qRT-PCR. Relative gene expression determinations were made with the comparative delta CT normalized to GAPDH expression (P = 0.001). b According to the median ratio of relative SPRY4-IT1 expression (0.535) in tumor tissues, SPRY4-IT1 expression was classified into two groups: relative high-SPRY4-IT1 group (n = 30, red column) and relative low- SPRY4-IT1 group (n = 31, blue column). Data was presented as fold-change in tumor tissues relative to normal tissues (P = 0.001). c, d Kaplan–Meier overall survival and disease-free survival curves according to SPRY4-IT1 expression level. Patients with decreased SPRY4-IT1 expression (n = 31) showed reduced survival times compared with patients with high level of SPRY4-IT1 expression (n = 31) (P = 0.001 or 0.002, log-rank test).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522960&req=5

Fig1: Relative SPRY4-IT1 expression and its clinical significance in gastric cancer tissues. a SPRY4-IT1 expression in matched cancerous tissues and adjacent noncancerous tissues from 61 gastric cancer patients were measured by qRT-PCR. Relative gene expression determinations were made with the comparative delta CT normalized to GAPDH expression (P = 0.001). b According to the median ratio of relative SPRY4-IT1 expression (0.535) in tumor tissues, SPRY4-IT1 expression was classified into two groups: relative high-SPRY4-IT1 group (n = 30, red column) and relative low- SPRY4-IT1 group (n = 31, blue column). Data was presented as fold-change in tumor tissues relative to normal tissues (P = 0.001). c, d Kaplan–Meier overall survival and disease-free survival curves according to SPRY4-IT1 expression level. Patients with decreased SPRY4-IT1 expression (n = 31) showed reduced survival times compared with patients with high level of SPRY4-IT1 expression (n = 31) (P = 0.001 or 0.002, log-rank test).
Mentions: We firstly examined SPRY4-IT1 expression level in 61 paired gastric cancer samples and adjacent normal tissues using qRT-PCR approach, and gene expression was calculated relative to that of an internal control (ΔCt). As shown in Fig. 1a, 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.Fig. 1

Bottom Line: Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry.Differences between groups were tested for significance using Student's t test (two-tailed).Patients with lower SPRY4-IT1 expression had a relatively poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China. 1115769204@qq.com.

ABSTRACT

Background: Long 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.

Methods: QRT-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).

Results: SPRY4-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.

Conclusion: Low 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.

No MeSH data available.


Related in: MedlinePlus