title: Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.
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.
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Yan
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Tong
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Sun
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Sun
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Sun
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Meng
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pathology, Third Affiliated Clinical Hospital, Harbin Medical University, Harbin, China.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Cell Biology & Anatomy, University of Calgary, Alberta, Canada.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Songbin
authors.initials: S
authors.lastname: Fu
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D005353:Fibronectins; C000608558:RPL22L1 protein, human; C000608557:RPL22L1 protein, mouse; D012269:Ribosomal Proteins; D014746:Vimentin; D051176:beta Catenin