Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer.
Neighboring genes transcribing in the same direction can form chimeric RNAs via cis-splicing (cis-SAGe). Previously, we reported 16 novel cis-SAGe chimeras in prostate cancer cell lines, and performed in silico validation on 14 pairs of normal and tumor samples from Chinese patients. However, whether these fusions exist in different populations, as well as their clinical implications, remains unclear. To investigate, we developed a bioinformatics pipeline using modified Spliced Transcripts Alignment to a Reference (STAR) to quantify these fusion RNAs simultaneously in silico. From RNA-Seq data of 100 paired normal and prostate cancer samples from TCGA, we find that most fusions are not specific to cancer. However, D2HGDH-GAL3ST2 is more frequently seen in cancer samples, and seems to be enriched in the African American group. Further validation with our own collection as well as from commercial sources did not detect this fusion RNA in 29 normal prostate samples, but in 19 of 93 prostate cancer samples. It is more frequently detected in late stage cancer, suggesting a role in cancer progression. Consistently, silencing this fusion resulted in dramatic reduction of cell proliferation rate and cell motility.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908.
Fujun
F
Qin
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908; Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, China.
Zhenguo
Z
Song
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908.
Maxwell
M
Chang
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908.
Yansu
Y
Song
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908.
Henry
H
Frierson
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908. Electronic address: hl9r@virginia.edu.
Hui
H
Li
D001741:Black or African American / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012326:RNA Splicing; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D044465:White People / Q000235:genetics
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D000429:Alcohol Oxidoreductases; C558760:D2HGDH protein, human; D013466:Sulfurtransferases; C432419:GAL3ST2 protein, human; D015238:Sulfotransferases
Chimeric RNA; D2HGDH-GAL3ST2; Prostate cancer; STAR; cis-SAGe