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Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis

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Abstract

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.

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References

  1. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30

    Article  PubMed  Google Scholar 

  2. Culine S, El Demery M, Lamy PJ, Iborra F, Avances C, Pinguet F (2007) Docetaxel and cisplatin in patients with metastatic androgen independent prostate cancer and circulating neuroendocrine markers. J Urol 178(3):844–848. doi:10.1016/j.juro.2007.05.044

    Article  CAS  PubMed  Google Scholar 

  3. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE (2001) Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 47(4):293–303. doi:10.1002/pros.1074.abs

    Article  CAS  PubMed  Google Scholar 

  4. Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM (2004) Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene 23(8):1599–1607. doi:10.1038/sj.onc.1207284

    Article  CAS  PubMed  Google Scholar 

  5. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. CMLS 65 (11):1631–1652. doi:10.1007/s00018-008-7452-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sun M, Estrov Z, Ji Y, Coombes KR, Harris DH, Kurzrock R (2008) Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther 7(3):464–473. doi:10.1158/1535-7163.MCT-07-2272

    Article  CAS  PubMed  Google Scholar 

  7. Saini S, Arora S, Majid S, Shahryari V, Chen Y, Deng GR, Yamamura S, Ueno K, Dahiya R (2011) Curcumin modulates MicroRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev Res 4(10):1698–1709. doi:10.1158/1940-6207.CAPR-11-0267

    Article  CAS  Google Scholar 

  8. Li X, Xie W, Xie C, Huang C, Zhu J, Liang Z, Deng F, Zhu M, Zhu W, Wu R, Wu J, Geng S, Zhong C (2014) Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. PTR 28(10):1553–1560. doi:10.1002/ptr.5167

    CAS  PubMed  Google Scholar 

  9. Saini S, Arora S, Majid S, Shahryari V, Chen Y, Deng G, Yamamura S, Ueno K, Dahiya R (2011) Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev Res (Phila) 4(10):1698–1709. doi:10.1158/1940-6207.CAPR-11-0267

    Article  CAS  PubMed Central  Google Scholar 

  10. Zhang JA, Du YP, Wu CG, Ren XL, Ti XY, Shi JR, Zhao F, Yin H (2010) Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186 signaling pathway. Oncol Rep 24(5):1217–1223. doi:10.3892/or_00000975

    CAS  PubMed  Google Scholar 

  11. Ambs S, Prueitt RL, Yi M, Hudson RS, Howe TM, Petrocca F, Wallace TA, Liu CG, Volinia S, Calin GA, Yfantis HG, Stephens RM, Croce CM (2008) Genomic profiling of MicroRNA and messenger RNA reveals deregulated MicroRNA expression in prostate cancer. Cancer Res 68(15):6162–6170. doi:10.1158/0008-5472.CAN-08-0144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhou P, Chen W-G, Li X-W (2015) MicroRNA-143 acts as a tumor suppressor by targeting hexokinase 2 in human prostate cancer. Am J Cancer Res 5(6):2056

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang JH, Ying GG, Wang JC, Jung YH, Lu JA, Zhu JA, Pienta KJ, Taichman RS (2010) Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression. Cancer Res 70(2):471–480. doi:10.1158/0008-5472.CAN-09-2863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Singh PK, Mehla K, Hollingsworth MA, Johnson KR (2011) Regulation of Aerobic Glycolysis by microRNAs in Cancer. Mol Cell Pharmacol 3(3):125–134

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Jordan BC, Mock CD, Thilagavathi R, Selvam C (2016) Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment. Life Sci 152:135–144. doi:10.1016/j.lfs.2016.03.036

    Article  CAS  PubMed  Google Scholar 

  16. Abel EV, Aplin AE (2010) FOXD3 is a mutant B-RAF-regulated inhibitor of G1-S progression in melanoma cells. Cancer Res 70(7):2891–2900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. Elife. doi:10.7554/eLife.05005

    Google Scholar 

  18. Mathelier A, Fornes O, Arenillas DJ, Chen CY, Denay G, Lee J, Shi W, Shyr C, Tan G, Worsley-Hunt R, Zhang AW, Parcy F, Lenhard B, Sandelin A, Wasserman WW (2016) JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles. Nucleic Acids Res 44(D1):D110–D115. doi:10.1093/nar/gkv1176

    Article  PubMed  Google Scholar 

  19. He ZY, Shi CB, Wen H, Li FL, Wang BL, Wang J (2011) Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest 29(3):208–213. doi:10.3109/07357907.2010.550592

    Article  CAS  PubMed  Google Scholar 

  20. Fu SQ, Kurzrock R (2010) Development of curcumin as an epigenetic agent. Cancer Am Cancer Soc 116 (20):4670–4676. doi:10.1002/cncr.25414

    CAS  Google Scholar 

  21. Bao B, Ali S, Banerjee S, Wang ZW, Logna F, Azmi AS, Kong DJ, Ahmad A, Li YW, Padhye S, Sarkar FH (2012) Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res 72(1):335–345. doi:10.1158/0008-5472.CAN-11-2182

    Article  CAS  PubMed  Google Scholar 

  22. Bryant RJ, Pawlowski T, Catto JWF, Marsden G, Vessella RL, Rhees B, Kuslich C, Visakorpi T, Hamdy FC (2012) Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 106(4):768–774. doi:10.1038/bjc.2011.595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ozen M, Creighton CJ, Ozdemir M, Ittmann M (2008) Widespread deregulation of microRNA expression in human prostate cancer. Oncogene 27(12):1788–1793. doi:10.1038/sj.onc.1210809

    Article  CAS  PubMed  Google Scholar 

  24. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, Nenutil R, Vyzula R (2007) Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology-Basel 72(5–6):397–402. doi:10.1159/000113489

    CAS  Google Scholar 

  25. Gao W, Yu Y, Cao H, Shen H, Li X, Pan S, Shu Y (2010) Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. Biomed Pharmacother 64(6):399–408

    Article  CAS  PubMed  Google Scholar 

  26. Jiang S, Zhang LF, Zhang HW, Hu S, Lu MH, Liang S, Li B, Li Y, Li DS, Wang ED, Liu MF (2012) A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. Embo J 31(8):1985–1998. doi:10.1038/emboj.2012.45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Clape C, Fritz V, Henriquet C, Apparailly F, Fernandez PL, Iborra F, Avances C, Villalba M, Culine S, Fajas L (2009) miR-143 Interferes with ERK5 signaling, and abrogates prostate cancer progression in mice. Plos One 4(10). doi:ARTN e754210.1371/journal.pone.0007542

  28. Bin X (2012) Mir-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of kras. Int J Urol 19:197–197

    Google Scholar 

  29. Hu H, Zhu W, Qin J, Chen M, Gong L, Li L, Liu X, Tao Y, Yin H, Zhou H (2017) Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hepatology 65(2):515–528

    Article  CAS  PubMed  Google Scholar 

  30. Ameis HM, Drenckhan A, von Loga K, Escherich G, Wenke K, Izbicki JR, Reinshagen K, Gros SJ (2013) PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma. Plos One 8(12):e83701

    Article  PubMed  PubMed Central  Google Scholar 

  31. Li X, Jiang Y, Meisenhelder J, Yang W, Hawke DH, Zheng Y, Xia Y, Aldape K, He J, Hunter T (2016) Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis. Mol Cell 61(5):705–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Schneider CC, Archid R, Fischer N, Bühler S, Venturelli S, Berger A, Burkard M, Kirschniak A, Bachmann R, Königsrainer A (2015) Metabolic alteration–Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics. Int J Surg 22:92–98

    Article  PubMed  Google Scholar 

  33. Wang J, Ying G, Wang J, Jung Y, Lu J, Zhu J, Pienta KJ, Taichman RS (2010) Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression. Cancer Res 70(2):471–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Romanuik TL, Ueda T, Le N, Haile S, Yong TM, Thomson T, Vessella RL, Sadar MD (2009) Novel biomarkers for prostate cancer including noncoding transcripts. Am J Pathol 175(6):2264–2276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liu LL, Lu SX, Li M, Li LZ, Fu J, Hu W, Yang YZ, Luo RZ, Zhang CZ, Yun JP (2014) FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2. Oncotarget 5(13):5113–5124. doi:10.18632/oncotarget.2089

    Article  PubMed  PubMed Central  Google Scholar 

  36. He G, Hu J, Zhou L, Zhu X, Xin S, Zhang D, Lu G, Liao W, Ding Y, Liang L (2016) The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer. Br J Cancer 115(11):1367–1378

    CAS  Google Scholar 

  37. Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV, Peterson KL, Indolfi C, Catalucci D, Chen J (2009) The knockout of miR-143 and-145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Diff 16(12):1590–1598

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by Project for Key Disease Type of Chinese and Western Integrative Medicine, Shanghai Municipal Commission of Heath and Family Planning: Special Subject Construction of Treating Prostatic Cancer by Chinese and Western Integrative Medicine (Subject Number: ZXBZ2012-07); Project of Establishing Working Studio of Shanghai Doctor of Traditional Chinese Medicine, Zhou Zhiheng (Subject Number: ZYSNXD-CC-MZY011); The three year plan of Shanghai to further accelerate the development of traditional Chinese Medicine (No: ZY3-RCPY-3-1012). We thank Shanghai Doctor of Traditional Chinese Medicine, Professor Zhiheng Zhou for his help.

Author contributions

HWC, HJY, and YGF carried out the experiments, participated in the statistical analysis, and drafted the manuscript; FL and LC conceived of the study, and participated in its design and coordination, and helped to draft the manuscript.

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    Authors and Affiliations

    1. Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China

      Hongwen Cao, Yigeng Feng & Lei Chen

    2. Oncology Department of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine Affiliated PUTUO Hospital, No. 164 Lanxi Road, Putuo District, Shanghai, 200062, China

      Hongjie Yu & Fang Liang

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    1. Hongwen Cao
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    Correspondence to Lei Chen or Fang Liang.

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    This study was supported by Project for Key Disease Type of Chinese and Western Integrative Medicine, Shanghai Municipal Commission of Heath and Family Planning: Special Subject Construction of Treating Prostatic Cancer by Chinese and Western Integrative Medicine (Subject Number: ZXBZ2012-07); Project of Establishing Working Studio of Shanghai Doctor of Traditional Chinese Medicine, Zhou Zhiheng (Subject Number: ZYSNXD-CC-MZY011); The three year plan of Shanghai to further accelerate the development of traditional Chinese Medicine (No: ZY3-RCPY-3-1012).

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    Hongwen Cao, Hongjie Yu, and Yigeng Feng contributed equally.

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    Cao, H., Yu, H., Feng, Y. et al. Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis. Cancer Chemother Pharmacol 79, 985–994 (2017). https://doi.org/10.1007/s00280-017-3301-1

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