Knockdown of SIX4 inhibits pancreatic cancer cells via apoptosis induction
Mohammad Heiat1, Ehsan Rezaei2, Javad Gharechahi3
1Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Abstract:
Sine oculis homeobox 4 (SIX4), a critical transcription factor modulating organ development, potentially participates in tumorigenesis through numerous pathways. Here, we investigated siRNA-mediated knockdown effects of SIX4 on pancreatic cancer cells and underlying molecular mechanisms. The expression of SIX4 in pancreatic cancer and adjacent tissues were investigated in clinical tissue samples and bioinformatically approved by gene expression omnibus (GEO) database. Appropriate siRNA transfected into PANC1 pancreatic cancer cells in order to SIX4 knockdown. The survival, migration, invasion, colony formation, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle in the cancer cells were investigated after knockdown of SIX4. In addition, expression of genes involved in apoptosis and metastasis were assessed in the transfected cancer cells in mRNA and protein levels. High-throughput analysis using GEO database confirmed the overexpression of SIX4 in pancreatic cancer tissues by six independent pancreatic cancer microarrays. Knockdown of SIX4 by specific siRNA significantly decreased survival, colony formation, and mitochondrial membrane potential of the cancer cells. Further assessments demonstrated that knockdown of SIX4 increases the apoptosis and autophagy rates in the cancer cells through modifying the expression of related genes. Moreover, a significant decrease in migration and invasion rates were observed in SIX4 suppressed group. Furthermore, frequency of the cells transfected with SIX4 siRNA increased slightly in G1 and Sub-G1 phases of cell cycle. Our study suggested that siRNA-mediated knockdown of SIX4 increases the pancreatic cancer cells death and reduces the invasion and migration of the cancer cells through different molecular pathways.
Insights
Knocking down Sine oculis homeobox 4 (SIX4) in pancreatic cancer cells reduces cell survival, colony formation, and metastasis. This SIX4 suppression also increases apoptosis and autophagy, offering potential therapeutic strategies for pancreatic cancer.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Sine oculis homeobox 4 (SIX4) is a transcription factor involved in organ development and potentially tumorigenesis.
- Overexpression of SIX4 has been observed in pancreatic cancer tissues.
- Understanding SIX4's role is crucial for developing targeted pancreatic cancer therapies.
Purpose of the Study:
- To investigate the effects of siRNA-mediated knockdown of SIX4 on pancreatic cancer cells.
- To elucidate the molecular mechanisms underlying SIX4's role in pancreatic cancer progression.
- To assess the therapeutic potential of targeting SIX4 in pancreatic cancer.
Main Methods:
- SIX4 expression analysis in clinical pancreatic cancer tissues and GEO database.
- siRNA-mediated knockdown of SIX4 in PANC1 pancreatic cancer cells.
- Assessment of cell survival, migration, invasion, apoptosis, autophagy, and cell cycle.
- Analysis of apoptosis and metastasis-related gene expression at mRNA and protein levels.
Main Results:
- SIX4 overexpression confirmed in pancreatic cancer tissues via GEO database analysis.
- SIX4 knockdown significantly reduced cell survival, colony formation, and mitochondrial membrane potential.
- SIX4 suppression increased apoptosis and autophagy rates by altering related gene expression.
- Reduced migration and invasion observed in SIX4-knockdown cells.
- Slight increase in G1 and Sub-G1 cell cycle phases noted after SIX4 knockdown.
Conclusions:
- siRNA-mediated knockdown of SIX4 effectively reduces pancreatic cancer cell viability and metastatic potential.
- Targeting SIX4 influences apoptosis, autophagy, and cell cycle progression in pancreatic cancer cells.
- SIX4 represents a potential therapeutic target for inhibiting pancreatic cancer growth and spread.
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