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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 was amplified on DMs and over-expressed in UACC-1598 cells.(A) Representative pictures of metaphase chromosomes of UACC-1598 and normal human lymphocytes. Arrows indicate DMs in UACC-1598 cells (magnification, ×1,000). (B) Representative images of FISH analysis. Metaphase chromosomes of UACC-1598 and human lymphocytes were detected with DNA probes. (a) Red probe indicates RPL22L1 and (b) green probe indicates MYCN; (c) both probes were located at the same locus on DMs as indicated by the arrows, (d) red probe indicates RPL22L1 in normal human lymphocytes (magnification, ×1,000). (C) DNA amplification levels of RPL22L1 detected by PCR, (D) RT-PCR result of mRNA expression levels of RPL22L1 in different samples.
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pone.0143659.g001: RPL22L1 was amplified on DMs and over-expressed in UACC-1598 cells.(A) Representative pictures of metaphase chromosomes of UACC-1598 and normal human lymphocytes. Arrows indicate DMs in UACC-1598 cells (magnification, ×1,000). (B) Representative images of FISH analysis. Metaphase chromosomes of UACC-1598 and human lymphocytes were detected with DNA probes. (a) Red probe indicates RPL22L1 and (b) green probe indicates MYCN; (c) both probes were located at the same locus on DMs as indicated by the arrows, (d) red probe indicates RPL22L1 in normal human lymphocytes (magnification, ×1,000). (C) DNA amplification levels of RPL22L1 detected by PCR, (D) RT-PCR result of mRNA expression levels of RPL22L1 in different samples.

Mentions: The OC cell line UACC-1598 contained amplified genes in the form of DMs. Oncogene amplification on DMs is representative of tumorigenesis, but does not occur in normal cells (Fig 1A). Using a FISH analysis, we detected amplified regions of RPL22L1 that co-localized with MYCN on DMs (Fig 1B). Furthermore, we detected the amplification of RPL22L1 in normal ovarian tissues, human lymphocytes, and UACC-1598 cells using PCR (Fig 1C). We also examined the amplification of RPL22L1 in another three ovarian cancer cell lines (S1 Fig). RT-PCR confirmed the expression of RPL22L1 in different samples (Fig 1D). These results indicated that RPL22L1 was amplified via DMs in UACC-1598 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)

RPL22L1 was amplified on DMs and over-expressed in UACC-1598 cells.(A) Representative pictures of metaphase chromosomes of UACC-1598 and normal human lymphocytes. Arrows indicate DMs in UACC-1598 cells (magnification, ×1,000). (B) Representative images of FISH analysis. Metaphase chromosomes of UACC-1598 and human lymphocytes were detected with DNA probes. (a) Red probe indicates RPL22L1 and (b) green probe indicates MYCN; (c) both probes were located at the same locus on DMs as indicated by the arrows, (d) red probe indicates RPL22L1 in normal human lymphocytes (magnification, ×1,000). (C) DNA amplification levels of RPL22L1 detected by PCR, (D) RT-PCR result of mRNA expression levels of RPL22L1 in different samples.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0143659.g001: RPL22L1 was amplified on DMs and over-expressed in UACC-1598 cells.(A) Representative pictures of metaphase chromosomes of UACC-1598 and normal human lymphocytes. Arrows indicate DMs in UACC-1598 cells (magnification, ×1,000). (B) Representative images of FISH analysis. Metaphase chromosomes of UACC-1598 and human lymphocytes were detected with DNA probes. (a) Red probe indicates RPL22L1 and (b) green probe indicates MYCN; (c) both probes were located at the same locus on DMs as indicated by the arrows, (d) red probe indicates RPL22L1 in normal human lymphocytes (magnification, ×1,000). (C) DNA amplification levels of RPL22L1 detected by PCR, (D) RT-PCR result of mRNA expression levels of RPL22L1 in different samples.
Mentions: The OC cell line UACC-1598 contained amplified genes in the form of DMs. Oncogene amplification on DMs is representative of tumorigenesis, but does not occur in normal cells (Fig 1A). Using a FISH analysis, we detected amplified regions of RPL22L1 that co-localized with MYCN on DMs (Fig 1B). Furthermore, we detected the amplification of RPL22L1 in normal ovarian tissues, human lymphocytes, and UACC-1598 cells using PCR (Fig 1C). We also examined the amplification of RPL22L1 in another three ovarian cancer cell lines (S1 Fig). RT-PCR confirmed the expression of RPL22L1 in different samples (Fig 1D). These results indicated that RPL22L1 was amplified via DMs in UACC-1598 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