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Abstract
Gene expression is controlled at the transcriptional and post-transcriptional levels. The TACC2 gene was known to be associated with tumors but the control of its expression is unclear. We have reported that activity of the intronic promoter p10 of TACC2 in primary lesion of endometrial cancer is indicative of lymph node metastasis among a low-risk patient group. Here, we analyze the intronic promoter derived isoforms in JHUEM-1 endometrial cancer cells, and primary tissues of endometrial cancers and normal endometrium. Full-length cDNA amplicons are produced by long-range PCR and subjected to nanopore sequencing followed by computational error correction. We identify 16 stable, 4 variable, and 9 rare exons including 3 novel exons validated independently. All variable and rare exons reside N-terminally of the TACC domain and contribute to isoform variety. We found 240 isoforms as high-confidence, supported by more than 20 reads. The large number of isoforms produced from one minor promoter indicates the post-transcriptional complexity coupled with transcription at the TACC2 locus in cancer and normal cells.
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1 Juntendo University, Faculty of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.258269.2) (ISNI:0000 0004 1762 2738); RIKEN Center for Integrative Medical Sciences, Preventive Medicine and Applied Genomics Unit, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267)
2 Juntendo University, Faculty of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.258269.2) (ISNI:0000 0004 1762 2738)
3 RIKEN Center for Integrative Medical Sciences, Laboratory for Comprehensive Genomic Analysis, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267)
4 Juntendo University, Faculty of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.258269.2) (ISNI:0000 0004 1762 2738); Nucleic Acid Diagnostic System Development Unit, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Diagnostics and Therapeutics of Intractable Diseases, Tokyo, Japan (GRID:grid.258269.2) (ISNI:0000 0004 1762 2738)
5 RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255)
6 RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255); RIKEN Center for Integrative Medical Sciences, Laboratory for Advanced Genomics Circuit, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267)
7 RIKEN Center for Integrative Medical Sciences, Preventive Medicine and Applied Genomics Unit, Yokohama, Japan (GRID:grid.509459.4) (ISNI:0000 0004 0472 0267); RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama, Japan (GRID:grid.7597.c) (ISNI:0000000094465255); Tokyo Metropolitan Institute of Medical Science, Research Center for Genome & Medical Sciences, Tokyo, Japan (GRID:grid.272456.0)