Skip to main content

Advertisement

SpringerLink
Log in

Research on the Effect and Mechanism of Selenium on Colorectal Cancer Through TRIM32

  • Research
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The intake of selenium (Se) in the human body is negatively correlated with the risk of colorectal cancer (CRC), but its mechanism in the occurrence and development of CRC is not clear. This study aimed to evaluate the therapeutic effect of Se on CRC, and explore the anti-tumor effect of Se supplementation on CRC and its molecular mechanism. In this study, we utilized colony formation assay, cell scratch test, Transwell migration, and flow cytometry to assess cell proliferation, migration, and apoptosis. Our findings demonstrate that Se effectively suppresses the growth and proliferation of CRC cell lines HCT116 and SW480 and promoting cellular apoptosis. In vivo experiments demonstrated a significant inhibitory effect of Se on tumor growth. CRC-related datasets were extracted from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases for differential expression analysis of TRIM32 and survival analysis. We found that TRIM32 was highly expressed in tumor tissues of CRC patients and correlated with a poor prognosis. Furthermore, through RNA sequencing analysis, we identified TRIM32 as a gene that was significantly decreased after Se treatment in HCT116 cells. This finding was subsequently validated by Western blot results. Moreover, TRIM32 knockdown combined with Se treatment significantly inhibited cell growth proliferation and migration and further induced apoptosis of colorectal cancer cells. In conclusion, our findings provided evidence that Se inhibited the growth of colorectal cancer cells by down-regulating TRIM32.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66(4):683–691. https://doi.org/10.1136/gutjnl-2015-310912

    Article  PubMed  Google Scholar 

  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660

    Article  CAS  PubMed  Google Scholar 

  3. Siegel RL, Wagle NS, Cercek A, Smith RA (2023) Jemal A (2023) Colorectal cancer statistics. CA Cancer J Clin 73(3):233–254. https://doi.org/10.3322/caac.21772

    Article  PubMed  Google Scholar 

  4. Nordberg M, Nordberg GF (2016) Trace element research-historical and future aspects. J Trace Elem Med Bio 38:46–52. https://doi.org/10.1016/j.jtemb.2016.04.006

    Article  CAS  Google Scholar 

  5. Rayman MP (2000) The importance of selenium to human health. The Lancet 356(9225):233–241. https://doi.org/10.1016/S0140-6736(00)02490-9

    Article  CAS  Google Scholar 

  6. Kielczykowska M, Kocot J, Pazdzior M, Musik I (2018) Selenium - a fascinating antioxidant of protective properties. Adv Clin Exp Med 27(2):245–255. https://doi.org/10.17219/acem/67222

    Article  PubMed  Google Scholar 

  7. Kieliszek M (2019) Selenium(-) fascinating microelement, properties and sources in food. Molecules 24(7). https://doi.org/10.3390/molecules24071298

  8. Vinceti M, Filippini T, Del GC, Dennert G, Zwahlen M, Brinkman M, Zeegers MP, Horneber M, D’Amico R, Crespi CM (2018) Selenium for preventing cancer. Cochrane Database Syst Rev 1:D5195. https://doi.org/10.1002/14651858.CD005195.pub4

    Article  Google Scholar 

  9. Fedirko V, Jenab M, Meplan C, Jones JS, Zhu W, Schomburg L, Siddiq A, Hybsier S, Overvad K, Tjonneland A, Omichessan H, Perduca V, Boutron-Ruault MC, Kuhn T, Katzke V, Aleksandrova K, Trichopoulou A, Karakatsani A, Kotanidou A, Tumino R, Panico S, Masala G, Agnoli C, Naccarati A, Bueno-De-Mesquita B, Vermeulen R, Weiderpass E, Skeie G, Nost TH, Lujan-Barroso L, Quiros JR, Huerta JM, Rodriguez-Barranco M, Barricarte A, Gylling B, Harlid S, Bradbury KE, Wareham N, Khaw KT, Gunter M, Murphy N, Freisling H, Tsilidis K, Aune D, Riboli E, Hesketh JE, Hughes DJ (2019) Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status. Nutrients 11(4) https://doi.org/10.3390/nu11040935

  10. Kudva AK, Shay AE, Prabhu KS (2015) Selenium and inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 309(2):G71–G77. https://doi.org/10.1152/ajpgi.00379.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ye R, Huang J, Wang Z, Chen Y, Dong Y (2021) Trace element selenium effectively alleviates intestinal diseases. Int J Mol Sci 22(21):11708. https://doi.org/10.3390/ijms222111708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Watanabe M, Hatakeyama S (2017) TRIM proteins and diseases. J Biochem 161(2):135–144. https://doi.org/10.1093/jb/mvw087

    Article  CAS  PubMed  Google Scholar 

  13. Hatakeyama S (2017) TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci 42(4):297–311. https://doi.org/10.1016/j.tibs.2017.01.002

    Article  CAS  PubMed  Google Scholar 

  14. Eberhardt W, Haeussler K, Nasrullah U, Pfeilschifter J (2020) Multifaceted roles of TRIM proteins in colorectal carcinoma. Int J Mol Sci 21(20). https://doi.org/10.3390/ijms21207532

  15. Marzano F, Caratozzolo MF, Pesole G, Sbisa E, Tullo A (2021) TRIM proteins in colorectal cancer: TRIM8 as a promising therapeutic target in chemo resistance. Biomedicines 9(3) https://doi.org/10.3390/biomedicines9030241

  16. Liu M, Zhang X, Cai J, Li Y, Luo Q, Wu H, Yang Z, Wang L, Chen D (2018) Downregulation of TRIM58 expression is associated with a poor patient outcome and enhances colorectal cancer cell invasion. Oncol Rep 40(3):1251–1260. https://doi.org/10.3892/or.2018.6525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lazzari E, Meroni G (2016) TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: from muscular dystrophy to tumours. Int J Biochem Cell Biol 79:469–477. https://doi.org/10.1016/j.biocel.2016.07.023

    Article  CAS  PubMed  Google Scholar 

  18. Cambiaghi V, Giuliani V, Lombardi S, Marinelli C, Toffalorio F, Pelicci PG (2012) TRIM proteins in cancer. Adv Exp Med Biol 770:77–91. https://doi.org/10.1007/978-1-4614-5398-7_6

    Article  CAS  PubMed  Google Scholar 

  19. Locke M, Tinsley CL, Benson MA, Blake DJ (2009) TRIM32 is an E3 ubiquitin ligase for dysbindin. Hum Mol Genet 18(13):2344–2358. https://doi.org/10.1093/hmg/ddp167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ito M, Migita K, Matsumoto S, Wakatsuki K, Tanaka T, Kunishige T, Nakade H, Nakatani M, Nakajima Y (2017) Overexpression of E3 ubiquitin ligase tripartite motif 32 correlates with a poor prognosis in patients with gastric cancer. Oncol Lett 13(5):3131–3138. https://doi.org/10.3892/ol.2017.5806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang C, Xu J, Fu H, Zhang Y, Zhang X, Yang D, Zhu Z, Wei Z, Hu Z, Yan R, Cai Q (2018) TRIM32 promotes cell proliferation and invasion by activating β-catenin signalling in gastric cancer. J Cell Mol Med 22(10):5020–5028. https://doi.org/10.1111/jcmm.13784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhao T, Jin F, Li J, Xu Y, Dong H, Liu Q, Xing P, Zhu G, Xu H, Yin S, Miao Z (2018) TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway. J Cancer 9(8):1349–1356. https://doi.org/10.7150/jca.22390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yin H, Li Z, Chen J, Hu X (2019) Expression and the potential functions of TRIM32 in lung cancer tumorigenesis. J Cell Biochem 120(4):5232–5243. https://doi.org/10.1002/jcb.27798

    Article  CAS  PubMed  Google Scholar 

  24. Su X, Wang B, Wang Y, Wang B (2020) Inhibition of TRIM32 induced by miR-519d increases the sensitivity of colorectal cancer cells to cisplatin. Onco Targets Ther 13:277–289. https://doi.org/10.2147/OTT.S235940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W (2022) Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl) 135(5):584–590. https://doi.org/10.1097/CM9.0000000000002108

    Article  PubMed  Google Scholar 

  26. Dariya B, Aliya S, Merchant N, Alam A, Nagaraju GP (2020) Colorectal cancer biology, diagnosis, and therapeutic approaches. Crit Rev Oncog 25(2):71–94. https://doi.org/10.1615/CritRevOncog.2020035067

    Article  PubMed  Google Scholar 

  27. Wrobel JK, Power R, Toborek M (2016) Biological activity of selenium: revisited. IUBMB Life 68(2):97–105. https://doi.org/10.1002/iub.1466

    Article  CAS  PubMed  Google Scholar 

  28. Schrauzer GN (2009) Selenium and selenium-antagonistic elements in nutritional cancer prevention. Crit Rev Biotechnol 29(1):10–17. https://doi.org/10.1080/07388550802658048

    Article  CAS  PubMed  Google Scholar 

  29. Keskin H, Wang SM, Etemadi A, Fan JH, Dawsey SM, Abnet CC, Qiao YL, Taylor PR (2021) Colorectal cancer in the Linxian China Nutrition Intervention Trial: risk factors and intervention results. PLoS ONE 16(9):e255322. https://doi.org/10.1371/journal.pone.0255322

    Article  CAS  Google Scholar 

  30. Hesketh J, Meplan C (2011) Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar. Proc Nutr Soc 1–9. https://doi.org/10.1017/S0029665111000115

  31. Meplan C, Hesketh J (2012) The influence of selenium and selenoprotein gene variants on colorectal cancer risk. Mutagenesis 27(2):177–186. https://doi.org/10.1093/mutage/ger058

    Article  CAS  PubMed  Google Scholar 

  32. Wang H, Liu H, Zhou M, Shi H, Shen M (2020) Correlations between 13 trace elements and circulating tumor cells in patients with colorectal cancer in Guangzhou China. Biol Trace Elem Res 198(1):58–67. https://doi.org/10.1007/s12011-020-02061-7

    Article  CAS  PubMed  Google Scholar 

  33. Meplan C, Johnson IT, Polley AC, Cockell S, Bradburn DM, Commane DM, Arasaradnam RP, Mulholland F, Zupanic A, Mathers JC, Hesketh J (2016) Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. Faseb J 30(8):2812–2825. https://doi.org/10.1096/fj.201600251R

    Article  CAS  PubMed  Google Scholar 

  34. Pohl NM, Tong C, Fang W, Bi X, Li T, Yang W (2009) Transcriptional regulation and biological functions of selenium-binding protein 1 in colorectal cancer in vitro and in nude mouse xenografts. PLoS ONE 4(11):e7774. https://doi.org/10.1371/journal.pone.0007774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang X, Hong R, Bei L, Yang J, Zhao X, Hu Z, Chen L, Meng H, Zhang Q, Niu G, Yue Y, Ke C (2022) Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the delta-like ligand 4/Notch1 signaling pathway. Transl Oncol 18:101365. https://doi.org/10.1016/j.tranon.2022.101365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Jaworska AM, Wlodarczyk NA, Mackiewicz A, Czerwinska P (2020) The role of TRIM family proteins in the regulation of cancer stem cell self-renewal. Stem Cells 38(2):165–173. https://doi.org/10.1002/stem.3109

    Article  CAS  PubMed  Google Scholar 

  37. Han Y, Tan Y, Zhao Y, Zhang Y, He X, Yu L, Jiang H, Lu H, Tian H (2020) TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer. J Cell Mol Med 24(10):5491–5500. https://doi.org/10.1111/jcmm.15203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Horn EJ, Albor A, Liu Y, El-Hizawi S, Vanderbeek GE, Babcock M, Bowden GT, Hennings H, Lozano G, Weinberg WC, Kulesz-Martin M (2004) RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties. Carcinogenesis 25(2):157–167. https://doi.org/10.1093/carcin/bgh003

    Article  CAS  PubMed  Google Scholar 

  39. Zhang B, Yan YY, Gu YQ, Teng F, Lin X, Zhou XL, Che JX, Dong XW, Zhou LX, Lin NM (2022) Inhibition of TRIM32 by ibr-7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway. J Cell Mol Med 26(2):515–526. https://doi.org/10.1111/jcmm.17109

    Article  CAS  PubMed  Google Scholar 

  40. Wang J, Fang Y, Liu T (2020) TRIM32 promotes the growth of gastric cancer cells through enhancing AKT activity and glucose transportation. Biomed Res Int 2020:4027627. https://doi.org/10.1155/2020/4027627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Liu J, Zhang C, Wang XL, Ly P, Belyi V, Xu-Monette ZY, Young KH, Hu W, Feng Z (2014) E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis. Cell Death Differ 21(11):1792–1804. https://doi.org/10.1038/cdd.2014.121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kano S, Miyajima N, Fukuda S, Hatakeyama S (2008) Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2. Cancer Res 68(14):5572–5580. https://doi.org/10.1158/0008-5472.CAN-07-6231

    Article  CAS  PubMed  Google Scholar 

  43. Prajapati P, Gohel D, Shinde A, Roy M, Singh K, Singh R (2020) TRIM32 regulates mitochondrial mediated ROS levels and sensitizes the oxidative stress induced cell death. Cell Signal 76:109777. https://doi.org/10.1016/j.cellsig.2020.109777

    Article  CAS  PubMed  Google Scholar 

  44. Soukupova K, Rudolf E (2019) Suppression of proliferation and activation of cell death by sodium selenite involves mitochondria and lysosomes in chemoresistant bladder cancer cells. J Trace Elem Med Biol 52:58–67. https://doi.org/10.1016/j.jtemb.2018.11.009

    Article  CAS  PubMed  Google Scholar 

  45. Jeong JY, Wang Y, Sytkowski AJ (2009) Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium-dependent manner. Biochem Biophys Res Commun 379(2):583–588. https://doi.org/10.1016/j.bbrc.2008.12.110

    Article  CAS  PubMed  Google Scholar 

  46. Fontelles CC, Ong TP (2017) Selenium and breast cancer risk: focus on cellular and molecular mechanisms. Adv Cancer Res 136:173–192. https://doi.org/10.1016/bs.acr.2017.08.001

    Article  CAS  PubMed  Google Scholar 

  47. Saeed AM, Mohamed HR, Ahmed KM (2019) The pro-oxidant, apoptotic and anti-angiogenic effects of selenium supplementation on colorectal tumors induced by 1,2-dimethylhydrazine in BALB/C mice. Rep Biochem Mol Biol 8(3):216–226

    Google Scholar 

Download references

Acknowledgements

We thank the associate editor and the reviewers for their useful feedback that improved this paper.

Funding

This study was financially supported by National Natural Science Foundation of China (no. 82073414) and Basic and Applied Basic Research Foundation of Guangdong Province (no. 2021A1515010715).

Author information

Authors and Affiliations

  1. Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China

    Xiaohua Cai, Yintong Su, Jiayu Ning, Xingxing Fan & Mei Shen

Authors
  1. Xiaohua Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yintong Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiayu Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xingxing Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mei Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Xiaohua Cai: Conceptualization, Methodology, Investigation, Writing – original draft, Writing – review & editing, Project administration. Yintong Su: Investigation, Methodology, Formal analysis. Jiayu Ning: Validation, Formal analysis. Xingxing Fan: Resources. Mei Shen: Conceptualization, Supervision, Writing – review & editing, Funding acquisition. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mei Shen.

Ethics declarations

Ethics Approval

The study was reviewed and approved by the Medical Ethics Committee of Southern Medical University (no. 2021–0024) and the Experimental Animal Ethics Committee of Southern Medical University (L2019074).

Consent to Participate

All study participants signed informed consent.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 651 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, X., Su, Y., Ning, J. et al. Research on the Effect and Mechanism of Selenium on Colorectal Cancer Through TRIM32. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04206-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12011-024-04206-4

Keywords

Search

Navigation