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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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RPL22L1 promoted OC cell migration and invasion.(A-D) Representative pictures of wound-healing assay of cells (magnification, ×40). (E-H) Migration of cells was detected by transwell migration assay, and (I-L) cell invasion was evaluated using a Matrigel invasion chamber. Examples of cells that migrated through the membrane (left panel), columns indicate triplicate experiments (magnification, ×100, Bar: mean ± SD * P < 0.05, independent Student’s t-test).
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pone.0143659.g004: RPL22L1 promoted OC cell migration and invasion.(A-D) Representative pictures of wound-healing assay of cells (magnification, ×40). (E-H) Migration of cells was detected by transwell migration assay, and (I-L) cell invasion was evaluated using a Matrigel invasion chamber. Examples of cells that migrated through the membrane (left panel), columns indicate triplicate experiments (magnification, ×100, Bar: mean ± SD * P < 0.05, independent Student’s t-test).

Mentions: To confirm the role of RPL22L1 in OC cells, UACC-1598 cells were treated with three specific siRNAs against RPL22L1 (siRNA-1, siRNA-2, and siRNA-3). Since siRNA-2 exhibited the most efficient knockdown of endogenous RPL22L1, it was chosen for subsequent analyses (S3 Fig). Except SKOV3-RPL22L1 and the control cells, we used another two OC cell lines HO-8910 and HO-8910PM with lower RPL22L1 expression to transient transfected with RPL22L1 for further functional study (S3 Fig). The effect of RPL22L1 on cell motility was characterized by wound-healing, transwell migration, and Matrigel invasion assays. Knockdown of RPL22L1 in UACC-1598 cells (1598-siRPL22L1) caused clear ression of cells migration and invasion. Over-expression of RPL22L1 in SKOV3-RPL22L1, HO-8910 (8910-RPL22L1), and HO-8910PM (8910PM-RPL22L1) cells could significantly enhance cells migration and invasion (P < 0.05, Fig 4). Cell growth rate was analyzed by an MTA assay, RPL22L1 had no influence on cell proliferation (data not shown). These results suggested that high level of RPL22L1 enhances OC cells migration and invasion.


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)

RPL22L1 promoted OC cell migration and invasion.(A-D) Representative pictures of wound-healing assay of cells (magnification, ×40). (E-H) Migration of cells was detected by transwell migration assay, and (I-L) cell invasion was evaluated using a Matrigel invasion chamber. Examples of cells that migrated through the membrane (left panel), columns indicate triplicate experiments (magnification, ×100, Bar: mean ± SD * P < 0.05, independent Student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0143659.g004: RPL22L1 promoted OC cell migration and invasion.(A-D) Representative pictures of wound-healing assay of cells (magnification, ×40). (E-H) Migration of cells was detected by transwell migration assay, and (I-L) cell invasion was evaluated using a Matrigel invasion chamber. Examples of cells that migrated through the membrane (left panel), columns indicate triplicate experiments (magnification, ×100, Bar: mean ± SD * P < 0.05, independent Student’s t-test).
Mentions: To confirm the role of RPL22L1 in OC cells, UACC-1598 cells were treated with three specific siRNAs against RPL22L1 (siRNA-1, siRNA-2, and siRNA-3). Since siRNA-2 exhibited the most efficient knockdown of endogenous RPL22L1, it was chosen for subsequent analyses (S3 Fig). Except SKOV3-RPL22L1 and the control cells, we used another two OC cell lines HO-8910 and HO-8910PM with lower RPL22L1 expression to transient transfected with RPL22L1 for further functional study (S3 Fig). The effect of RPL22L1 on cell motility was characterized by wound-healing, transwell migration, and Matrigel invasion assays. Knockdown of RPL22L1 in UACC-1598 cells (1598-siRPL22L1) caused clear ression of cells migration and invasion. Over-expression of RPL22L1 in SKOV3-RPL22L1, HO-8910 (8910-RPL22L1), and HO-8910PM (8910PM-RPL22L1) cells could significantly enhance cells migration and invasion (P < 0.05, Fig 4). Cell growth rate was analyzed by an MTA assay, RPL22L1 had no influence on cell proliferation (data not shown). These results suggested that high level of RPL22L1 enhances OC cells migration and invasion.

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