title: Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing.
abstract: Gene fusion is among the primary processes that generate new genes and has been well characterized as potent pathway of oncogenesis. Here, by high-throughput RNA sequencing in nine paired human endometrial carcinoma (EC) and matched non-cancerous tissues, we obtained that chimeric translin-associated factor X-disrupted-in-schizophrenia 1 (TSNAX-DISC1) occurred significantly upregulated in multiple EC samples. Experimental investigation showed that TSNAX-DISC1 appears to be formed by splicing without chromosomal rearrangement. The chimera expression inversely correlated with the binding of CCCTC-binding factor (CTCF) to the insulators. Subsequent investigations indicate that long intergenic non-coding RNA lincRNA-NR_034037, separating TSNAX from DISC1, regulates TSNAX -DISC1 production and TSNAX/DISC1 expression levels by extricating CTCF from insulators. Dysregulation of TSNAX influences steroidogenic factor-1-stimulated transcription on the StAR promoter, altering progesterone actions, implying the association with cancer. Together, these results advance our understanding of the mechanism in which lincRNA-NR_034037 regulates TSNAX-DISC1 formation programs that tightly regulate EC development.
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and.
authors.forename: Xun
authors.initials: X
authors.lastname: Lan
authors.affiliation: The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou 215123, China, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China, Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA and The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China zhouyifeng@suda.edu.cn.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D000076246:CCCTC-Binding Factor; D002453:Cell Cycle; D049109:Cell Proliferation; D002648:Child; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C498305:TSNAX protein, human