期刊
CARCINOGENESIS
卷 35, 期 12, 页码 2687-2697出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgu201
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资金
- 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]
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.
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