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Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.

Wu N, Wei J, Wang Y, Yan J, Qin Y, Tong D, Pang B, Sun D, Sun H, Yu Y, Sun W, Meng X, Zhang C, Bai J, Chen F, Geng J, Lee KY, Fu S, Jin Y - PLoS ONE (2015)

Bottom Line: RPL22L1 inhibition reduced expression of vimentin and N-cadherin.These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT).It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

ABSTRACT
Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

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DNA copy number and expression level of RPL22L1 in clinical OC samples.(A) DNA copy number profiles of RPL22L1 in an ovarian serous cystadenocarcinoma data set registered in the Oncomine database (TCGA Ovarian 2 Dataset). Two independent microarray gene expression datasets (B) GSE29405 and (C) GSE27651 from GEO website were used to examine the expression level of RPL22L1 in OC. The raw.CEL files for the two databases were downloaded and normalized by RMA. RPL22L1 was more highly expressed in OC than in normal ovarian tissue (* P < 0.05, independent Student’s t-test). Representative pictures of RPL22L1 protein expression in (D) OC and (E) matched adjacent normal tissue by IHC (magnification, ×400).
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pone.0143659.g002: DNA copy number and expression level of RPL22L1 in clinical OC samples.(A) DNA copy number profiles of RPL22L1 in an ovarian serous cystadenocarcinoma data set registered in the Oncomine database (TCGA Ovarian 2 Dataset). Two independent microarray gene expression datasets (B) GSE29405 and (C) GSE27651 from GEO website were used to examine the expression level of RPL22L1 in OC. The raw.CEL files for the two databases were downloaded and normalized by RMA. RPL22L1 was more highly expressed in OC than in normal ovarian tissue (* P < 0.05, independent Student’s t-test). Representative pictures of RPL22L1 protein expression in (D) OC and (E) matched adjacent normal tissue by IHC (magnification, ×400).

Mentions: To determine the amplification of RPL22L1 in clinical, we used the Oncomine database (https://www.oncomine.org) to analyze the DNA copy number profiles of the RPL22L1 in a TCGA ovarian dataset (TCGA Ovarian 2, http://tcga-data.nci.nih.gov/tcga/) [20, 21]. This dataset clearly indicated a significant increase in the DNA copy number of RPL22L1 in OC compared to normal blood and ovarian tissues, threshold by P < 10−4 (Fig 2A).


Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.

Wu N, Wei J, Wang Y, Yan J, Qin Y, Tong D, Pang B, Sun D, Sun H, Yu Y, Sun W, Meng X, Zhang C, Bai J, Chen F, Geng J, Lee KY, Fu S, Jin Y - PLoS ONE (2015)

DNA copy number and expression level of RPL22L1 in clinical OC samples.(A) DNA copy number profiles of RPL22L1 in an ovarian serous cystadenocarcinoma data set registered in the Oncomine database (TCGA Ovarian 2 Dataset). Two independent microarray gene expression datasets (B) GSE29405 and (C) GSE27651 from GEO website were used to examine the expression level of RPL22L1 in OC. The raw.CEL files for the two databases were downloaded and normalized by RMA. RPL22L1 was more highly expressed in OC than in normal ovarian tissue (* P < 0.05, independent Student’s t-test). Representative pictures of RPL22L1 protein expression in (D) OC and (E) matched adjacent normal tissue by IHC (magnification, ×400).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4664398&req=5

pone.0143659.g002: DNA copy number and expression level of RPL22L1 in clinical OC samples.(A) DNA copy number profiles of RPL22L1 in an ovarian serous cystadenocarcinoma data set registered in the Oncomine database (TCGA Ovarian 2 Dataset). Two independent microarray gene expression datasets (B) GSE29405 and (C) GSE27651 from GEO website were used to examine the expression level of RPL22L1 in OC. The raw.CEL files for the two databases were downloaded and normalized by RMA. RPL22L1 was more highly expressed in OC than in normal ovarian tissue (* P < 0.05, independent Student’s t-test). Representative pictures of RPL22L1 protein expression in (D) OC and (E) matched adjacent normal tissue by IHC (magnification, ×400).
Mentions: To determine the amplification of RPL22L1 in clinical, we used the Oncomine database (https://www.oncomine.org) to analyze the DNA copy number profiles of the RPL22L1 in a TCGA ovarian dataset (TCGA Ovarian 2, http://tcga-data.nci.nih.gov/tcga/) [20, 21]. This dataset clearly indicated a significant increase in the DNA copy number of RPL22L1 in OC compared to normal blood and ovarian tissues, threshold by P < 10−4 (Fig 2A).

Bottom Line: RPL22L1 inhibition reduced expression of vimentin and N-cadherin.These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT).It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

ABSTRACT
Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

Show MeSH
Related in: MedlinePlus