Skip to main content
Log in

Silencing RPL8 inhibits the progression of hepatocellular carcinoma by down-regulating the mTORC1 signalling pathway

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

This study aimed to explore the role of ribosomal protein L8 (RPL8) in controlling hepatocellular carcinoma (LIHC) development. We measured RPL8 expression, apoptosis, cell viability, proliferation, migration, invasion, glucose uptake, lactate production, and the ATP/ADP ratio of LIHC cells to investigate the effect of RPL8 on LIHC. Bioinformatic analysis was employed to analyse RPL8 expression and its potential mechanism in LIHC. RPL8 was upregulated in LIHC tissues and cells. RPL8 silencing accelerated apoptosis and suppressed viability, growth, and movement of LIHC cells. Additionally, RPL8 silencing inhibited glycolysis in LIHC cells. Bioinformatic analysis revealed that RPL8 is regulated by the upstream transcription factor upstream stimulating factor 1 (USF1) and activates the mTORC1 signalling pathway. USF1 overexpression eliminated the inhibitory effect of RPL8 silencing in LIHC cells. RPL8 overexpression increased cell growth, movement, and glycolysis in LIHC. However, inhibition of the mTORC1 signalling pathway eliminated the effect of RPL8 overexpression on LIHC cells. In conclusion, RPL8 may affect LIHC progression by regulating the mTORC1 signalling pathway.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, Gores G. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018. https://doi.org/10.1038/nrdp.2016.18.

    Article  PubMed  Google Scholar 

  3. de la Cruz J, Karbstein K, Woolford JL Jr. Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo. Annu Rev Biochem. 2015;84:93–129. https://doi.org/10.1146/annurev-biochem-060614-033917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lin Z, Peng R, Sun Y, Zhang L, Zhang Z. Identification of ribosomal protein family in triple-negative breast cancer by bioinformatics analysis. 2021. Biosci Rep. https://doi.org/10.1042/bsr20200869.

  5. Hanes J, Klaudiny J, Vonderkammer H, Scheit KH. Characterization by cDNA cloning of the mRNA of human ribosomal protein L8. Biochem Biophys Res Commun. 1993;197(3):1223–8. https://doi.org/10.1006/bbrc.1993.2607.

    Article  CAS  PubMed  Google Scholar 

  6. Swoboda RK, Somasundaram R, Caputo L, Ochoa EM, Gimotty PA, Marincola FM, Van Belle P, Barth S, Elder D, Guerry D, Czerniecki B, Schuchter L, Vonderheide RH, Herlyn D. Shared MHC class II–dependent melanoma ribosomal protein L8 identified by phage display. Can Res. 2007;67(8):3555. https://doi.org/10.1158/0008-5472.can-06-2763.

    Article  CAS  Google Scholar 

  7. Futschik M, Jeffs A, Pattison S, Kasabov N, Sullivan M, Merrie A, Reeve A. Gene expression profiling of metastatic and nonmetastatic colorectal cancer cell lines. Genome Lett. 2002;1:26–34. https://doi.org/10.1166/gl.2002.005.

    Article  CAS  Google Scholar 

  8. Hwang K-A, Kwon JE, Noh Y, Park B, Jeong YJ, Lee S-M, Kim S-Y, Kim I, Kang SC. Effects of Zanthoxylum piperitum ethanol extract on osteoarthritis inflammation and pain. Biomed Pharmacother. 2018;105:481–90. https://doi.org/10.1016/j.biopha.2018.05.109.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang X, Wang S, Wang H, Cao J, Huang X, Chen Z, Xu P, Sun G, Xu J, Lv J, Xu Z. Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway. Mol Cancer. 2019;18(1):20. https://doi.org/10.1186/s12943-018-0935-5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ge Y, Li Q, Lin L, Jiang M, Shi L, Wang B, Yang L, Xu Z. Downregulation of NUSAP1 suppresses cell proliferation, migration, and invasion via inhibiting mTORC1 signalling pathway in gastric cancer. Cell Biochem Funct. 2020;38(1):28–37. https://doi.org/10.1002/cbf.3444.

    Article  CAS  PubMed  Google Scholar 

  11. Zhu L, Qin C, Li T, Ma X, Qiu Y, Lin Y, Ma D, Qin Z, Sun C, Shen X, Zhao Y, Han L. The E3 ubiquitin ligase TRIM7 suppressed hepatocellular carcinoma progression by directly targeting Src protein. Cell Death Differ. 2019;27:1–13. https://doi.org/10.1038/s41418-019-0464-9.

    Article  CAS  Google Scholar 

  12. Qiu J, Zhang S, Wang P, Wang H, Sha B, Peng H, Ju Z, Rao J, Lu L. BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway. Cancer Med. 2020;9(21):8159–72. https://doi.org/10.1002/cam4.3411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hu Y-W, Kang C-M, Zhao J-J, Nie Y, Zheng L, Li H-X, Li X, Wang Q, Qiu Y-R. LncRNA PLAC2 down-regulates RPL36 expression and blocks cell cycle progression in glioma through a mechanism involving STAT1. J Cell Mol Med. 2018;22(1):497–510. https://doi.org/10.1111/jcmm.13338.

    Article  CAS  PubMed  Google Scholar 

  14. Daftuar L, Zhu Y, Jacq X, Prives C. Ribosomal proteins RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network. PLoS ONE. 2013;8(7):e68667–e68667. https://doi.org/10.1371/journal.pone.0068667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kondoh N, Shuda M, Tanaka K, Wakatsuki T, Hada A, Yamamoto M. Enhanced expression of S8, L12, L23a, L27 and L30 ribosomal protein mRNAs in human hepatocellular carcinoma. Anticancer Res. 2001;21(4A):2429–33.

    CAS  PubMed  Google Scholar 

  16. Dong Z, Jiang H, Liang S, Wang Y, Jiang W, Zhu C. Ribosomal protein L15 is involved in colon carcinogenesis. Int J Med Sci. 2019;16(8):1132–41. https://doi.org/10.7150/ijms.34386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li J, Liu W, Hao H, Wang Q, Xue L. Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway. Oncol Lett. 2019;18(3):2694–703. https://doi.org/10.3892/ol.2019.10589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tian NY, Qi YJ, Hu Y, Yin B, Yuan JG, Qiang BQ, Peng XZ, Han W. RNA-binding protein UNR promotes glioma cell migration and regulates the expression of ribosomal protein L9. Chinese Med Sci J. 2018;33(3):143–51.

    Google Scholar 

  19. Wu H, Qiao M, Peng X, Wu J, Liu G, Sun H, Li L, Mei S. Molecular characterization, expression patterns, and association analysis with carcass traits of porcine USF1 gene. Appl Biochem Biotechnol. 2013;170(6):1310–9. https://doi.org/10.1007/s12010-013-0280-5.

    Article  CAS  PubMed  Google Scholar 

  20. Zhao X, Wang T, Liu B, Wu Z, Yu S, Wang T. Significant association between upstream transcription factor 1 rs2516839 polymorphism and hepatocellular carcinoma risk: a case–control study. Tumor Biology. 2015;36(4):2551–8. https://doi.org/10.1007/s13277-014-2871-3.

    Article  CAS  PubMed  Google Scholar 

  21. Yan H, He N, He S. HCG15 is a hypoxia-responsive lncRNA and facilitates hepatocellular carcinoma cell proliferation and invasion by enhancing ZNF641 transcription. Biochem Biophys Res Commun. 2022;608:170–6. https://doi.org/10.1016/j.bbrc.2022.03.143.

    Article  CAS  PubMed  Google Scholar 

  22. Chen B, Chen X-P, Wu M-S, Cui W, Zhong M. Expressions of heparanase and upstream stimulatory factor in hepatocellular carcinoma. Eur J Med Res. 2014;19(1):45. https://doi.org/10.1186/s40001-014-0045-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chaichanit N, Wonglapsuwan M, Chotigeat W. Ribosomal protein L10A and signaling pathway. Gene. 2018;674:170–7. https://doi.org/10.1016/j.gene.2018.06.081.

    Article  CAS  PubMed  Google Scholar 

  24. Huang Z, Zhang Y, Li H, Zhou Y, Zhang Q, Chen R, Jin T, Hu K, Li S, Wang Y, Chen W, Huang Z. Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3. Cell Death Dis. 2019;10(12):936–936. https://doi.org/10.1038/s41419-019-2177-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tandon P, Gallo CA, Khatri S, Barger JF, Yepiskoposyan H, Plas DR. Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency. Proc Natl Acad Sci. 2011;108(6):2361–5. https://doi.org/10.1073/pnas.1013629108.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Holz MK, Ballif BA, Gygi SP, Blenis J. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell. 2005;123(4):569–80. https://doi.org/10.1016/j.cell.2005.10.024.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yi Zheng.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Consent for publication

Not applicable.

Ethics approval and consent to participate

The protocol of this research has been approved by the Ethics Committee of The Second Affiliated Hospital of Zhejiang Chinese Medical University (No: 2021–0108). All patients have signed written informed consent.

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 (PDF 386 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

Sun, T., Zhu, W., Ru, Q. et al. Silencing RPL8 inhibits the progression of hepatocellular carcinoma by down-regulating the mTORC1 signalling pathway. Human Cell 36, 725–737 (2023). https://doi.org/10.1007/s13577-022-00852-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-022-00852-9

Keywords

Navigation