title: Integrated analysis of long noncoding RNAs and mRNAs reveals their potential roles in the pathogenesis of uterine leiomyomas.
abstract: Global expression profiling studies showed that miRNAs are aberrantly expressed in uterine leiomyomas (ULMs) and are involved in ULM pathogenesis. Long noncoding RNAs (lncRNAs) are another group of regulatory RNA whose expression and roles in ULMs have not been explored. In this study, we examined the global expressions of lncRNAs and mRNAs in ULMs using microarray and interrogated their interrelationship through co-expression analysis. We found that lncRNAs and mRNAs were dysregulated in ULMs and the degree of dysregulation was positively correlated with tumor size. Further analysis showed that lncRNAs correlate to their cis mRNAs in expression levels depending on genomic locations and orientations. Moreover, we identified several dysregulated pathways that were correlated to dysregulated lncRNAs. We validated several aberrantly expressed lncRNAs in extended samples and confirmed that AK023096 was down-regulated and chromatin-associated RNA (CAR) Intergenic 10 was up-regulated in the majority of leiomyomas. Knockdown of Intergenic 10 inhibited the proliferation of leiomyoma cells in vitro, indicating its functional importance in ULM pathogenesis. The neighboring protein-coding gene ADAM12 was also downregulated in Intergenic 10 knockdown leiomyoma cells. We showed for the first time that lncRNAs were dysregulated in uterine leiomyomas. Aberrantly expressed lncRNAs may contribute to the pathogenesis of uterine leiomyomas.
authors.affiliation: Department of Molecular Medicine and Genetics and Ministry of Education Key Laboratory of Experimental Teratology, Shandong University, Jinan, Shandong, China. These authors contributed equally to this work.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Molecular Medicine and Genetics and Ministry of Education Key Laboratory of Experimental Teratology, Shandong University, Jinan, Shandong, China. These authors contributed equally to this work.
authors.forename: Xiyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Ruifen
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Yinuo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Xiyao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular Medicine and Genetics and Ministry of Education Key Laboratory of Experimental Teratology, Shandong University, Jinan, Shandong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hou
authors.affiliation: Department of Pathology, Northwestern University School of Medicine, Chicago, IL,USA.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
authors.affiliation: Department of Molecular Medicine and Genetics and Ministry of Education Key Laboratory of Experimental Teratology, Shandong University, Jinan, Shandong, China.
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Molecular Medicine and Genetics and Ministry of Education Key Laboratory of Experimental Teratology, Shandong University, Jinan, Shandong, China. Department of Cell Biology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D012333:RNA, Messenger