title: ROR functions as a ceRNA to regulate Nanog expression by sponging miR-145 and predicts poor prognosis in pancreatic cancer.
abstract: lncRNAs have emerged as key regulators of tumor development and progression. ROR is a typical lncRNA that plays important regulatory roles in the pathogenesis and progression of tumors. Nevertheless, current understanding of the involvement of ROR in pancreatic adenocarcinoma tumorigenesis remains limited. In this study, we measured ROR in 61 paired cancerous and noncancerous tissue samples by qRT-PCR and investigated the biological role of ROR on the phenotypes of pancreatic cancer stem cells (PCSCs) in vitro and in vivo. The effects of ROR on PCSCs were studied by RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation. The positive ROR/Nanog interaction was identified and verified by immunohistochemistry assay. Compared with adjacent non-tumor tissues, ROR was up-regulated in most tumor tissues. Knockdown of ROR by RNA interference in PCSCs inhibited proliferation, induced apoptosis and decreased migration. Moreover, ROR silencing resulted in significantly decreased tumourigenicity of PCSCs in nude mice than controls. In particular, ROR may act as a ceRNA, effectively becoming a sink for miR-145, thereby activating the derepression of core transcription factors Nanog. In conclusions, we demonstrated that decreased ROR expression could inhibit cell proliferation, invasion, and tumourigenicity by modulating Nanog. Therefore, ROR is a potential novel prognostic marker to predict the clinical outcome of pancreatic cancer patients after surgery and may be a rational target for therapy.
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xi
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Luming
authors.initials: L
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D000071317:Nanog Homeobox Protein / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: C000588825:Linc-RNA-RoR, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm
keywords: Nanog; ROR; cancer stem cells; incRNA; microRNA