Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells

Karthik M. Kodigepalli, Pavana Anur, Paul Spellman, Peter J. Sims, Meera Nanjundan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. Genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. SnoN/SkiL) have been implicated in ovarian cancer pathophysiology. We have previously shown that SnoN expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (As2O3).Findings: We now demonstrate increased DNA copy number levels (TCGA data) of phospholipid scramblase 1 (PLSCR1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with SnoN mRNA. Interestingly, SnoN can modulate PLSCR1 mRNA levels in the absence/presence of interferon (IFN-2α). Both IFN-2α and As2O3 treatment can modulate PLSCR1 mRNA levels in ovarian carcinoma cells. However, SnoN siRNA does not lead to altered PLSCR1 protein implicating other events needed to modulate its protein levels. In addition, we report that PLSCR1 can modulate aspects of the As2O3 cellular response.Conclusions: Our findings warrant further investigation into the role of PLSCR1 in ovarian cancer development and chemoresistance.

Original languageEnglish (US)
Article number32
JournalMolecular Cancer
Volume12
Issue number1
DOIs
StatePublished - Apr 26 2013

Fingerprint

Phospholipid Transfer Proteins
Ovarian Neoplasms
Interferons
Messenger RNA
Genes
Drug Resistance
Small Interfering RNA
Proteins
Biomarkers
Carcinoma
Cell Line
arsenic trioxide
DNA

Keywords

  • 3q23
  • 3q26.2
  • Arsenic trioxide
  • Interferon
  • Ovarian cancer
  • Phospholipid scramblase
  • PLSCR1
  • SnoN/SkiL
  • TGF-β

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells. / Kodigepalli, Karthik M.; Anur, Pavana; Spellman, Paul; Sims, Peter J.; Nanjundan, Meera.

In: Molecular Cancer, Vol. 12, No. 1, 32, 26.04.2013.

Research output: Contribution to journalArticle

Kodigepalli, Karthik M. ; Anur, Pavana ; Spellman, Paul ; Sims, Peter J. ; Nanjundan, Meera. / Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells. In: Molecular Cancer. 2013 ; Vol. 12, No. 1.
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AB - Background: Treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. Genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. SnoN/SkiL) have been implicated in ovarian cancer pathophysiology. We have previously shown that SnoN expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (As2O3).Findings: We now demonstrate increased DNA copy number levels (TCGA data) of phospholipid scramblase 1 (PLSCR1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with SnoN mRNA. Interestingly, SnoN can modulate PLSCR1 mRNA levels in the absence/presence of interferon (IFN-2α). Both IFN-2α and As2O3 treatment can modulate PLSCR1 mRNA levels in ovarian carcinoma cells. However, SnoN siRNA does not lead to altered PLSCR1 protein implicating other events needed to modulate its protein levels. In addition, we report that PLSCR1 can modulate aspects of the As2O3 cellular response.Conclusions: Our findings warrant further investigation into the role of PLSCR1 in ovarian cancer development and chemoresistance.

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