Identification Of Chimeric Transcript TSNAX-DISC1in Endometrial Carcinoma Through RNA-Seq

As a prevalent class of mutations, fusion genes are resulting from intergenicsplicing between two adjacent genes conjoined into a single gene and can generate newtranscripts. Several fusion genes have been nominated as a potent pathway ofoncogenesis in many human cancers. However, whether fusion gene is implicated inendometrial carcinoma （EC） or not is unknown. Here, by paired-end transcriptomesequencing （RNA-Seq） in9paired human endometrial carcinoma and matchednon-cancerous tissues, we show that chimeric transcript TSNAX-DISC1located onchromosome1q42.2, an EC risk-related susceptibility locus, occurred in significantlyhigher level in multiple EC samples than in matched non-cancerous tissues. Based onreverse transcription PCR analysis, TSNAX-DISC1appears to be formed by intergenicsplicing of adjacent genes without chromosomal rearrangement. The binding ofCCCTC-binding factor （CTCF） to the insulator elements is inversely correlated with theexpression of the chimera. Subsequent investigations indicate that the long intergenicnoncoding RNA lincRNA-NR₀34037, separating TSNAX from the downstream DISC1,regulates chimeric TSNAX-DISC1production and TSNAX/DISC1expression levels byextricating CTCF from insulator elements. In addition, luciferase reporter and ChIPassays indicated that dysregulation of TSNAX significantly attenuated the binding ofTSNAX, Translin and SF-1formed a complex to the StAR promoter and modulated StARgene transcription. Together, these results advance our understanding of the mechanismin which lincRNA-NR₀34037regulates TSNAX-DISC1formation programs that tightlyregulate EC development.