Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing

Na Li; Jian Zheng; Hua Li; Jieqiong Deng; Min Hu; Hongchun Wu; Wei Li; Fang Li; Xun Lan; Jiachun Lu; Yifeng Zhou

doi:10.1093/carcin/bgu201

Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing

Carcinogenesis. 2014 Dec;35(12):2687-97. doi: 10.1093/carcin/bgu201. Epub 2014 Sep 19.

Authors

Na Li¹, Jian Zheng¹, Hua Li², Jieqiong Deng¹, Min Hu³, Hongchun Wu¹, Wei Li¹, Fang Li¹, Xun Lan⁴, Jiachun Lu⁵, Yifeng Zhou⁶

Affiliations

¹ 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.
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 and.
⁵ The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
⁶ 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.

PMID: 25239642
DOI: 10.1093/carcin/bgu201

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Aged
Animals
Apoptosis
Blotting, Western
CCCTC-Binding Factor
Cell Cycle
Cell Proliferation
Child
Chromatin Immunoprecipitation
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Endometrial Neoplasms / genetics*
Endometrial Neoplasms / metabolism
Endometrial Neoplasms / pathology*
Endometrium / metabolism
Female
Gene Rearrangement
High-Throughput Nucleotide Sequencing*
Humans
Immunoenzyme Techniques
Mice
Mice, Nude
Neoplasm Grading
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
RNA Splicing / genetics*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

CCCTC-Binding Factor
CTCF protein, human
Ctcf protein, mouse
DISC1 protein, human
DNA-Binding Proteins
Nerve Tissue Proteins
RNA, Messenger
Repressor Proteins
TSNAX protein, human