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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 enhanced intraperitoneal xenograft tumor development in vivo.(A) Expression of RPL22L1 in UACC-1598 and SKOV3 cells was examined by western blots. Expression of RPL22L1 in SKOV3-RPL22L1 and control cells was examined by (B) western blots and (C) qRT-PCR. (D) Four-week-old nude mice were intraperitoneally injected with SKOV3-RPL22L1 or control cells and bioluminescence images were taken after 30 days. (Bar: mean ± SD; * P < 0.05, independent Student’s t-test).
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pone.0143659.g003: RPL22L1 enhanced intraperitoneal xenograft tumor development in vivo.(A) Expression of RPL22L1 in UACC-1598 and SKOV3 cells was examined by western blots. Expression of RPL22L1 in SKOV3-RPL22L1 and control cells was examined by (B) western blots and (C) qRT-PCR. (D) Four-week-old nude mice were intraperitoneally injected with SKOV3-RPL22L1 or control cells and bioluminescence images were taken after 30 days. (Bar: mean ± SD; * P < 0.05, independent Student’s t-test).

Mentions: To detect the role of high level RPL22L1 in tumor progression, we selected an OC cell line with low RPL22L1 expression, SKOV3, for further functional studies (Fig 3A). SKOV3 cells were stable transfection with luciferase previously and then stable transfection with RPL22L1 (Fig 3B and 3C). To explore the role of RPL22L1 in tumor progression in vivo, we intraperitoneally injected SKOV3-RPL22L1 and control cells into nude mice. The xenografted tumors were measured using bioluminescence at the 30th day after injection, area of xenograft tumor in mice with SKOV3-RPL22L1 cells injected was larger than that of control cells injected (Fig 3D). The result suggested that high level of RPL22L1 contribute to tumor development.


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 enhanced intraperitoneal xenograft tumor development in vivo.(A) Expression of RPL22L1 in UACC-1598 and SKOV3 cells was examined by western blots. Expression of RPL22L1 in SKOV3-RPL22L1 and control cells was examined by (B) western blots and (C) qRT-PCR. (D) Four-week-old nude mice were intraperitoneally injected with SKOV3-RPL22L1 or control cells and bioluminescence images were taken after 30 days. (Bar: mean ± SD; * P < 0.05, independent Student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0143659.g003: RPL22L1 enhanced intraperitoneal xenograft tumor development in vivo.(A) Expression of RPL22L1 in UACC-1598 and SKOV3 cells was examined by western blots. Expression of RPL22L1 in SKOV3-RPL22L1 and control cells was examined by (B) western blots and (C) qRT-PCR. (D) Four-week-old nude mice were intraperitoneally injected with SKOV3-RPL22L1 or control cells and bioluminescence images were taken after 30 days. (Bar: mean ± SD; * P < 0.05, independent Student’s t-test).
Mentions: To detect the role of high level RPL22L1 in tumor progression, we selected an OC cell line with low RPL22L1 expression, SKOV3, for further functional studies (Fig 3A). SKOV3 cells were stable transfection with luciferase previously and then stable transfection with RPL22L1 (Fig 3B and 3C). To explore the role of RPL22L1 in tumor progression in vivo, we intraperitoneally injected SKOV3-RPL22L1 and control cells into nude mice. The xenografted tumors were measured using bioluminescence at the 30th day after injection, area of xenograft tumor in mice with SKOV3-RPL22L1 cells injected was larger than that of control cells injected (Fig 3D). The result suggested that high level of RPL22L1 contribute to tumor development.

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