Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells

P Pramoonjago1, A S Baras, C A Moskaluk

  • 1Department of Pathology and Biochemistry, University of Virginia, Charlottesville, VA 22908, USA.

Oncogene
|April 26, 2006
PubMed

Insights

Sox4 gene expression is elevated in adenoid cystic carcinoma (ACC). Downregulating Sox4 (Sry-related high mobility group box 4) significantly increased apoptosis and reduced cell viability in ACC cells, suggesting Sox4 promotes cancer survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Expression Analysis

Background:

  • Sox4 (Sry-related high mobility group box 4) is significantly upregulated in adenoid cystic carcinoma (ACC) compared to normal tissues.
  • Elevated Sox4 expression suggests a potential role in ACC pathogenesis.

Purpose of the Study:

  • To investigate the functional significance of Sox4 in ACC.
  • To determine if Sox4 contributes to the malignant phenotype of ACC cells.

Main Methods:

  • Immunohistochemistry was used to assess Sox4 protein levels in primary ACC tissues and normal controls.
  • RNA interference (RNAi) was employed to downregulate Sox4 expression in the ACC3 cell line.
  • Microarray gene expression profiling was performed on cells with Sox4 knockdown.

Main Results:

  • Sox4 protein was confirmed to be upregulated in ACC tissues.
  • Downregulation of Sox4 in ACC3 cells led to a 51% reduction in cell viability and an 85% increase in apoptosis.
  • Sox4 knockdown modulated the expression of genes involved in apoptosis and cell cycle control.
  • The pro-apoptotic effects of Sox4 knockdown were reversible with Sox4 re-expression.

Conclusions:

  • Sox4 plays a crucial role in promoting cell survival in ACC.
  • Targeting Sox4 may represent a potential therapeutic strategy for adenoid cystic carcinoma.

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...