Related Experiment Video
Updated: May 1, 2026
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Gene expression profiling associated with angiotensin II type 2 receptor-induced apoptosis in human prostate cancer
Nana Pei1, Feilong Jie1, Jie Luo1
1School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Abstract:
Increased expression of angiotensin II type 2 receptor (AT2R) induces apoptosis in numerous tumor cell lines, with either Angiotensin II-dependent or Angiotensin II-independent regulation, but its molecular mechanism remains poorly understood. Here, we used PCR Array analysis to determine the gene and microRNA expression profiles in human prostate cancer cell lines transduced with AT2R recombinant adenovirus. Our results demonstrated that AT2R over expression leads to up-regulation of 6 apoptosis-related genes (TRAIL-R2, BAG3, BNIPI, HRK, Gadd45a, TP53BP2), 2 cytokine genes (IL6 and IL8) and 1 microRNA, and down-regulation of 1 apoptosis-related gene TNFSF10 and 2 cytokine genes (BMP6, BMP7) in transduced DU145 cells. HRK was identified as an up-regulated gene in AT2R-transduced PC-3 cells by real-time RT-PCR. Next, we utilized siRNAs to silence the up-regulated genes to further determine their roles on AT2R overexpression mediated apoptosis. The results showed downregulation of Gadd45a reduced the apoptotic effect by ∼30% in DU145 cells, downregulation of HRK reduced AT2R-mediated apoptosis by more than 50% in PC-3 cells, while downregulation of TRAIL-R2 enhanced AT2R-mediated apoptosis more than 4 times in DU145 cells. We also found that the effects on AT2R-mediated apoptosis caused by downregulation of Gadd45a, TRAIL-R2 and HRK were independent in activation of p38 MAPK, p44/42 MAPK and p53. Taken together, our results demonstrated that TRAIL-R2, Gadd45a and HRK may be novel target genes for further study of the mechanism of AT2R-mediated apoptosis in prostate cancer cells.
Insights
Angiotensin II type 2 receptor (AT2R) overexpression induces prostate cancer cell death. Key genes like TRAIL-R2, Gadd45a, and HRK were identified as crucial mediators of this AT2R-driven apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The angiotensin II type 2 receptor (AT2R) is known to induce apoptosis in cancer cells, but its precise molecular mechanisms are not fully understood.
- Understanding AT2R's role in apoptosis is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the gene and microRNA expression profiles in prostate cancer cells overexpressing AT2R.
- To identify specific genes and microRNAs involved in AT2R-mediated apoptosis.
Main Methods:
- Utilized PCR Array analysis to profile gene and microRNA expression in AT2R-transduced human prostate cancer cell lines (DU145 and PC-3).
- Employed real-time RT-PCR to confirm gene upregulation.
- Used siRNAs to silence specific upregulated genes and assess their impact on AT2R-mediated apoptosis.
- Investigated the involvement of MAPK and p53 signaling pathways.
Main Results:
- AT2R overexpression upregulated apoptosis-related genes (TRAIL-R2, BAG3, BNIPI, HRK, Gadd45a, TP53BP2) and downregulated others (TNFSF10).
- HRK was identified as upregulated in PC-3 cells; Gadd45a and TRAIL-R2 were significant in DU145 cells.
- Silencing Gadd45a reduced apoptosis by ~30%, HRK by >50%, while silencing TRAIL-R2 enhanced apoptosis over 4-fold.
- The effects of Gadd45a, TRAIL-R2, and HRK were independent of p38 MAPK, p44/42 MAPK, and p53 activation.
Conclusions:
- TRAIL-R2, Gadd45a, and HRK are identified as novel target genes potentially involved in AT2R-mediated apoptosis in prostate cancer.
- These findings provide new insights into the molecular mechanisms of AT2R's pro-apoptotic function in prostate cancer.
