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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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The expression level of RPL22L1 influences OC cell line EMT.(A) Western blots showed lower levels of epithelial markers (E-cadherin, β-catenin, and α-catenin) and higher levels of mesenchymal markers (vimentin, α-SMA, and fibronectin) in SKOV3-RPL22L1 compared with in control cells. (B) IF analysis showed decreased levels of epithelial markers (α-catenin and β-catenin) and increased levels of mesenchymal markers (fibronectin and vimentin). (C) Western blot analysis showed that knockdown of RPL22L1 by siRNA resulted in a decreased level of mesenchymal markers (vimentin and N-cadherin) in UACC-1598 cells.
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pone.0143659.g005: The expression level of RPL22L1 influences OC cell line EMT.(A) Western blots showed lower levels of epithelial markers (E-cadherin, β-catenin, and α-catenin) and higher levels of mesenchymal markers (vimentin, α-SMA, and fibronectin) in SKOV3-RPL22L1 compared with in control cells. (B) IF analysis showed decreased levels of epithelial markers (α-catenin and β-catenin) and increased levels of mesenchymal markers (fibronectin and vimentin). (C) Western blot analysis showed that knockdown of RPL22L1 by siRNA resulted in a decreased level of mesenchymal markers (vimentin and N-cadherin) in UACC-1598 cells.

Mentions: It has become increasingly clear that EMT is an integral component of the progression of epithelial-derived tumors [22, 23]. We found that SKOV3-RPL22L1 cells exhibited a spindle-shaped and fibroblastic morphology whereas 1598-siRPL22L1 cells exhibited shrinkage shapes and increased cell–cell adhesion (S4 Fig). Therefore, we examined whether RPL22L1 induced EMT could account for the RPL22L1-mediated changes in cells motility and invasion. Biochemical hallmarks of EMT include the loss of expression of epithelial marker proteins and concurrent increase in mesenchymal marker expression [22, 24]. Western blots and immunofluorescence analyses were used to evaluate the expression of epithelial and mesenchymal markers. After ectopic over-expression of RPL22L1 in SKOV3 cells, the expression of epithelial makers, such as E-cadherin, β-catenin, and α-catenin decreased, whereas the expression of vimentin, α-SMA, and fibronectin increased (Fig 5A and 5B). In 1598-siRPL22L1 cells, the expression levels of the mesenchymal markers vimentin and N-cadherin were degraded (Fig 5C). These results suggested that the expression level of RPL22L1 influences EMT in OC cells.


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)

The expression level of RPL22L1 influences OC cell line EMT.(A) Western blots showed lower levels of epithelial markers (E-cadherin, β-catenin, and α-catenin) and higher levels of mesenchymal markers (vimentin, α-SMA, and fibronectin) in SKOV3-RPL22L1 compared with in control cells. (B) IF analysis showed decreased levels of epithelial markers (α-catenin and β-catenin) and increased levels of mesenchymal markers (fibronectin and vimentin). (C) Western blot analysis showed that knockdown of RPL22L1 by siRNA resulted in a decreased level of mesenchymal markers (vimentin and N-cadherin) in UACC-1598 cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0143659.g005: The expression level of RPL22L1 influences OC cell line EMT.(A) Western blots showed lower levels of epithelial markers (E-cadherin, β-catenin, and α-catenin) and higher levels of mesenchymal markers (vimentin, α-SMA, and fibronectin) in SKOV3-RPL22L1 compared with in control cells. (B) IF analysis showed decreased levels of epithelial markers (α-catenin and β-catenin) and increased levels of mesenchymal markers (fibronectin and vimentin). (C) Western blot analysis showed that knockdown of RPL22L1 by siRNA resulted in a decreased level of mesenchymal markers (vimentin and N-cadherin) in UACC-1598 cells.
Mentions: It has become increasingly clear that EMT is an integral component of the progression of epithelial-derived tumors [22, 23]. We found that SKOV3-RPL22L1 cells exhibited a spindle-shaped and fibroblastic morphology whereas 1598-siRPL22L1 cells exhibited shrinkage shapes and increased cell–cell adhesion (S4 Fig). Therefore, we examined whether RPL22L1 induced EMT could account for the RPL22L1-mediated changes in cells motility and invasion. Biochemical hallmarks of EMT include the loss of expression of epithelial marker proteins and concurrent increase in mesenchymal marker expression [22, 24]. Western blots and immunofluorescence analyses were used to evaluate the expression of epithelial and mesenchymal markers. After ectopic over-expression of RPL22L1 in SKOV3 cells, the expression of epithelial makers, such as E-cadherin, β-catenin, and α-catenin decreased, whereas the expression of vimentin, α-SMA, and fibronectin increased (Fig 5A and 5B). In 1598-siRPL22L1 cells, the expression levels of the mesenchymal markers vimentin and N-cadherin were degraded (Fig 5C). These results suggested that the expression level of RPL22L1 influences EMT in OC cells.

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