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Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis
Hongwen Cao1, Hongjie Yu2, Yigeng Feng1
1Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China.
Purpose:
Curcumin is a potent antitumor agent. The objective of this study was to explore the interaction between curcumin and PGK1, an oncogene in the FOXD3/miR-143 axis, in prostate cancer therapy.
Methods:
MiRNA microarray analysis was used to identify miRNAs upregulated by curcumin treatment. MiR-143 was dramatically upregulated by curcumin. Cells were treated with antimiR-143 in combination to curcumin, followed by examining cell viability and migration. Bioinformatics analysis was used to investigate target genes of miR-143. The interaction between miR-143 and PGK1 was evaluated with dual-luciferase assay. Since FOXD3 is important in the regulation of miR-143, we explored whether curcumin regulated FOXD3 expression. FOXD3 was also ectopically overexpressed to investigate its effects on curcumin's regulation of miR-143.
Results:
Curcumin treatment significantly upregulated miR-143 and decreased prostate cancer cell proliferation and migration. Those effects were attenuated by anti-miR-143 transfection. Both miR-143 overexpression and curcumin treatment inhibited PGK1 expression and ectopic expression of PGK1 antagonized curcumin's antitumor effects. FOXD3 was upregulated by miR-143. Ectopic expression of FOXD3 synergized with curcumin in upregulating miR-143 expression.
Conclusion:
Curcumin inhibits prostate cancer by upregulating miR-143. PGK1 is downregulated by miR-143, and FOXD3 upregulation is essential for the antitumor effect of curcumin.
Insights
Curcumin, a natural compound, fights prostate cancer by boosting miR-143, which lowers oncogene PGK1. FOXD3 is key to this antitumor effect.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Curcumin demonstrates significant antitumor properties.
- Prostate cancer remains a major health concern, necessitating novel therapeutic strategies.
- The FOXD3/miR-143 axis and its role in cancer are areas of active investigation.
Purpose of the Study:
- To investigate the therapeutic interaction between curcumin and phosphoglycerate kinase 1 (PGK1) in prostate cancer.
- To elucidate the role of miR-143 and FOXD3 in curcumin's antitumor effects.
- To explore the molecular mechanisms underlying curcumin's action in prostate cancer.
Main Methods:
- MiRNA microarray analysis to identify curcumin-modulated miRNAs.
- Cell viability and migration assays following anti-miR-143 treatment.
- Bioinformatics and dual-luciferase assays to confirm miR-143 targeting of PGK1.
- Investigation of FOXD3 regulation by curcumin and its impact on miR-143.
Main Results:
- Curcumin significantly upregulated miR-143, suppressing prostate cancer cell proliferation and migration.
- Anti-miR-143 treatment counteracted the inhibitory effects of curcumin.
- Both miR-143 and curcumin inhibited PGK1 expression; PGK1 overexpression reduced curcumin's efficacy.
- FOXD3 was upregulated by miR-143, and its ectopic expression enhanced curcumin's ability to upregulate miR-143.
Conclusions:
- Curcumin exerts its antitumor effects in prostate cancer primarily through the upregulation of miR-143.
- miR-143 directly downregulates the oncogene PGK1.
- FOXD3 plays a crucial role in mediating the antitumor activity of curcumin by enhancing miR-143 expression.