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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

The effect of SPRY4-IT1 on gastric cancer cells invasion and metastasis. a, b Transwell assays were used to investigate the changes in migratory and invasive abilities of BGC823 and SGC7901 cells transfected with pCDNA-SPRY4-IT1 or empty vector. c, d Analysis of an experimental metastasis was performed by injecting SPRY4-IT1-overexpressing BGC823 cells into nude mice. e Visualization of the entire lungs and HE-stained lung sections. *P < 0.05 and **P < 0.01.
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Fig4: The effect of SPRY4-IT1 on gastric cancer cells invasion and metastasis. a, b Transwell assays were used to investigate the changes in migratory and invasive abilities of BGC823 and SGC7901 cells transfected with pCDNA-SPRY4-IT1 or empty vector. c, d Analysis of an experimental metastasis was performed by injecting SPRY4-IT1-overexpressing BGC823 cells into nude mice. e Visualization of the entire lungs and HE-stained lung sections. *P < 0.05 and **P < 0.01.

Mentions: Cell invasion is a significant aspect of cancer progression, and involves the migration of tumor cells into contiguous tissues and the dissolution of extracellular matrix proteins. To investigate whether SPRY4-IT1 has a direct functional role in facilitating gastric cancer cell migration and invasion, we evaluated cancer cell migration and invasion through transwell assays. Increased SPRY4-IT1 expression levels impeded the migration of SGC7901 and BGC823 cells compared with controls. Similarly, invasion of SGC7901 and BGC823 cells was also reduced following up-regulation of SPRY4-IT1 expression (Fig. 4a, b). Conversely, knockdown of SPRY4-IT1 expression enhanced gastric cancer cells migration and invasion ability (Additional file 2: Figure 1D).Fig. 4


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)

The effect of SPRY4-IT1 on gastric cancer cells invasion and metastasis. a, b Transwell assays were used to investigate the changes in migratory and invasive abilities of BGC823 and SGC7901 cells transfected with pCDNA-SPRY4-IT1 or empty vector. c, d Analysis of an experimental metastasis was performed by injecting SPRY4-IT1-overexpressing BGC823 cells into nude mice. e Visualization of the entire lungs and HE-stained lung sections. *P < 0.05 and **P < 0.01.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: The effect of SPRY4-IT1 on gastric cancer cells invasion and metastasis. a, b Transwell assays were used to investigate the changes in migratory and invasive abilities of BGC823 and SGC7901 cells transfected with pCDNA-SPRY4-IT1 or empty vector. c, d Analysis of an experimental metastasis was performed by injecting SPRY4-IT1-overexpressing BGC823 cells into nude mice. e Visualization of the entire lungs and HE-stained lung sections. *P < 0.05 and **P < 0.01.
Mentions: Cell invasion is a significant aspect of cancer progression, and involves the migration of tumor cells into contiguous tissues and the dissolution of extracellular matrix proteins. To investigate whether SPRY4-IT1 has a direct functional role in facilitating gastric cancer cell migration and invasion, we evaluated cancer cell migration and invasion through transwell assays. Increased SPRY4-IT1 expression levels impeded the migration of SGC7901 and BGC823 cells compared with controls. Similarly, invasion of SGC7901 and BGC823 cells was also reduced following up-regulation of SPRY4-IT1 expression (Fig. 4a, b). Conversely, knockdown of SPRY4-IT1 expression enhanced gastric cancer cells migration and invasion ability (Additional file 2: Figure 1D).Fig. 4

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