Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells

P. Pramoonjago, A. S. Baras, C. A. Moskaluk

Research output: Contribution to journalArticlepeer-review

Abstract

Microarray RNA gene expression profiling analysis has shown that Sox4 (Sry-related high mobility group (HMG) box 4) is one of the most upregulated genes in adenoid cystic carcinoma (ACC), relative to non-neoplastic tissue of origin. Here, we show that Sox4 protein is similarly upregulated in ACC by immunohistochemistry of 28 primary cancers and 20 normal tissues. To elucidate the functional significance of these findings, RNA interference (RNAi)-mediated RNA silencing was used to downregulate Sox4 expression in the ACC-derived cell line, ACC3. With confirmed knockdown of Sox4 protein, cell viability was reduced by 51%, with a corresponding increase of apoptosis to 85% as compared to 12% in controls. Apoptosis was confirmed by cell morphology, DNA fragmentation and flow cytometry. Cells could be rescued from the proapoptotic effects of Sox4 RNAi by co-transfection with a construct expressing functional Sox4. Microarray gene expression profiling of RNAi knockdown experiments shows that downregulation of Sox4-modulated expression of critical genes involved in apoptosis and cell cycle control. Overall, our findings suggest that Sox4 contributes to the malignant phenotype of ACC cells by promoting cell survival.

Original languageEnglish (US)
Pages (from-to)5626-5639
Number of pages14
JournalOncogene
Volume25
Issue number41
DOIs
StatePublished - Sep 14 2006
Externally publishedYes

Keywords

  • Adenoid cystic carcinoma
  • Apoptosis
  • RNAi
  • Sox4

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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