机构：[1]Department of Genetics, Medical College of Soochow University, Suzhou 215123, China,[2]Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China,[3]Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China,[4]Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA[5]The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China
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.
基金：
National Scientific Foundation of China (81001278, 81171895,
81472630, 81072366, 81202040); Priority Academic Program
Development of Jiangsu Higher Education Institutions, Jiangsu
Provincial Natural Science Foundation (BK2011297); Jiangsu
Province Science and Technology Support Program (BE2012648);
Scientific Research Foundation for the Returned Overseas Chinese
Scholars, State Education Ministry (20101561); Suzhou Science and
Technology Development Plan (SYS201235); Beijing Municipal
Natural Science Foundation (7142167).
第一作者机构：[1]Department of Genetics, Medical College of Soochow University, Suzhou 215123, China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Genetics, Medical College of Soochow University, Suzhou 215123, China,
推荐引用方式(GB/T 7714)：
Na Li,Jian Zheng,Hua Li,et al.Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing[J].CARCINOGENESIS.2014,35(12):2687-97.doi:10.1093/carcin/bgu201.
APA：
Na Li,Jian Zheng,Hua Li,Jieqiong Deng,Min Hu...&Yifeng Zhou.(2014).Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing.CARCINOGENESIS,35,(12)
MLA：
Na Li,et al."Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing".CARCINOGENESIS 35..12(2014):2687-97
