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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
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Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer

Fujun Qin1, Zhenguo Song2, Maxwell Chang1

  • 1Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908.

Cancer Letters
|June 21, 2016
PubMed

Insights

Chimeric RNAs formed by cis-splicing (cis-SAGe) were analyzed in prostate cancer. The D2HGDH-GAL3ST2 fusion RNA is prevalent in late-stage cancer and promotes tumor growth and spread.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Neighboring genes can form chimeric RNAs through cis-splicing (cis-SAGe).
  • Previous research identified 16 novel cis-SAGe chimeras in prostate cancer cell lines and validated some in Chinese patient samples.
  • The prevalence and clinical significance of these chimeras in diverse populations remained largely unexplored.

Purpose of the Study:

  • To investigate the presence of previously identified cis-SAGe chimeras in a larger cohort of prostate cancer patients.
  • To determine the clinical implications and population-specific enrichment of these chimeric RNAs.
  • To validate the functional role of a specific chimera, D2HGDH-GAL3ST2, in prostate cancer progression.

Main Methods:

  • Development of a bioinformatics pipeline utilizing a modified Spliced Transcripts Alignment to a Reference (STAR) algorithm for simultaneous quantification of fusion RNAs.
  • In silico analysis of RNA-sequencing data from The Cancer Genome Atlas (TCGA) comprising 100 paired normal and prostate cancer samples.
  • Experimental validation using patient samples from diverse sources and functional assays (gene silencing).

Main Results:

  • Most identified cis-SAGe chimeras were not cancer-specific.
  • The D2HGDH-GAL3ST2 fusion RNA was significantly more frequent in prostate cancer samples compared to normal samples.
  • This fusion showed enrichment in the African American population and was associated with late-stage cancer, reduced cell proliferation, and decreased cell motility upon silencing.

Conclusions:

  • The D2HGDH-GAL3ST2 chimeric RNA is a potential biomarker for late-stage prostate cancer and may play a role in tumor progression.
  • Targeting this fusion could offer a therapeutic strategy for prostate cancer.
  • Further research is warranted to explore the clinical utility and mechanistic insights of cis-SAGe chimeras in cancer.
Keywords:
Chimeric RNAD2HGDH-GAL3ST2Prostate cancerSTARcis-SAGe

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