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MiR-342-3p inhibits LCSC oncogenicity and cell stemness through HDAC7/PTEN axis

Inflammation Research volume 71, pages 107–117 (2022)Cite this article

Abstract

Objective

This study aims to explore the effects of miR-342-3p on liver cancer stem cells (LCSC) and related mechanism.

Methods

LCSC were sorted using immunomagnetic beads and flow cytometry was used to determine CD133+ and CD133− sorted cells. The self-renewal ability and growth ability of LCSC were measured by tumor spheroid formation assay and soft agar colony formation assay. Protein and mRNA expressions of CD44, ALDH1, Bmi1, Sox2 and Oct4 were detected by western blot and quantitative PCR. The relationship between miR-342-3p and HDAC7 was analyzed by dual-luciferase assay. The acetylation level of H3 protein was measured by acetyl Lysine antibody.

Results

miR-342-3p overexpression in LCSC lead to lower tumor volume, reduced tumor spheroid formation and agar colony formation rates, as well as lower mRNA and protein expressions of CD44, ALDH1, Bmi1, Sox2, and Oct4. Dual-luciferase reporter assay confirmed HDAC7 as a target gene of miR-342-3p. Inhibition of HDAC7 or overexpression of PTEN suppressed the carcinogenicity and stemness of LCSC. PTEN expression was increased in sh-HDAC7 group and decreased in pcDNA3.1-HDAC7 group. HDAC7 promoted H3 deacetylation and inhibited PTEN expression. Overexpression of HDAC7 or silencing of PTEN could reverse the inhibitory effect of overexpression of miR-342-3p on LCSC carcinogenicity and cell stemness.

Conclusion

MiR-342-3p inhibited LCSC oncogenicity and cell stemness by promoting PTEN and inhibiting HDAC7.

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References

  1. Cheng Z, Li X, Ding J. Characteristics of liver cancer stem cells and clinical correlations. Cancer Lett. 2016;379:230–8.

    Article  CAS  Google Scholar 

  2. Meirelles Junior RF, Salvalaggio P, Rezende MB, Evangelista AS, Guardia BD, Matielo CE, et al. Liver transplantation: history, outcomes and perspectives. Einstein (Sao Paulo). 2015;13:149–52.

    Article  Google Scholar 

  3. Morise Z, Kawabe N, Tomishige H, Nagata H, Kawase J, Arakawa S, et al. Recent advances in the surgical treatment of hepatocellular carcinoma. World J Gastroenterol. 2014;20:14381–92.

    Article  Google Scholar 

  4. Liu W, Kang L, Han J, Wang Y, Shen C, Yan Z, et al. miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect. Onco Targets Ther. 2018;11:1643–53.

    Article  Google Scholar 

  5. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science. 2012;337:730–5.

    Article  CAS  Google Scholar 

  6. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012;21:283–96.

    Article  CAS  Google Scholar 

  7. Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J, Su H, et al. Crosstalk between long noncoding RNAs and microRNAs in health and disease. Int J Mol Sci. 2016;17:356.

    Article  Google Scholar 

  8. Si A, Wang L, Miao K, Zhang R, Ji H, Lei Z, et al. miR-219 regulates liver cancer stem cell expansion via E-cadherin pathway. Cell Cycle. 2019;18:3550–61.

    Article  CAS  Google Scholar 

  9. Gao Y, Zhang SG, Wang ZH, Liao JC. Down-regulation of miR-342-3p in hepatocellular carcinoma tissues and its prognostic significance. Eur Rev Med Pharmacol Sci. 2017;21:2098–102.

    CAS  PubMed  Google Scholar 

  10. Komoll RM, Hu Q, Olarewaju O, von Dohlen L, Yuan Q, Xie Y, et al. MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma. J Hepatol. 2021;74:122–34.

    Article  CAS  Google Scholar 

  11. Zhao J, Gray SG, Greene CM, Lawless MW. Unmasking the pathological and therapeutic potential of histone deacetylases for liver cancer. Expert Rev Gastroenterol Hepatol. 2019;13:247–56.

    Article  Google Scholar 

  12. Cutano V, Di Giorgio E, Minisini M, Picco R, Dalla E, Brancolini C. HDAC7-mediated control of tumour microenvironment maintains proliferative and stemness competence of human mammary epithelial cells. Mol Oncol. 2019;13:1651–68.

    Article  CAS  Google Scholar 

  13. Caslini C, Hong S, Ban YJ, Chen XS, Ince TA. HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells. Oncogene. 2019;38:6599–614.

    Article  CAS  Google Scholar 

  14. Xin X, Wu M, Meng Q, Wang C, Lu Y, Yang Y, et al. Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol Cancer. 2018;17:94.

    Article  Google Scholar 

  15. Xie L, Huang W, Fang Z, Ding F, Zou F, Ma X, et al. CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis. Cell Death Dis. 2019;10:751.

    Article  Google Scholar 

  16. Oliva-Gonzalez C, Uresti-Rivera EE, Galicia-Cruz OG, Jasso-Robles FI, Gandolfi AJ, Escudero-Lourdes C. The tumor suppressor phosphatase and tensin homolog protein (PTEN) is negatively regulated by NF-kappab p50 homodimers and involves histone 3 methylation/deacetylation in UROtsa cells chronically exposed to monomethylarsonous acid. Toxicol Lett. 2017;280:92–8.

    Article  CAS  Google Scholar 

  17. Sakamoto K, Iwasaki K, Sugiyama H, Tsuji Y. Role of the tumor suppressor PTEN in antioxidant responsive element-mediated transcription and associated histone modifications. Mol Biol Cell. 2009;20:1606–17.

    Article  Google Scholar 

  18. Burja B, Kuret T, Janko T, Topalovic D, Zivkovic L, Mrak-Poljsak K, et al. Olive leaf extract attenuates inflammatory activation and DNA damage in human arterial endothelial cells. Front Cardiovasc Med. 2019;6:56.

    Article  CAS  Google Scholar 

  19. Quan MF, Xiao LH, Liu ZH, Guo H, Ren KQ, Liu F, et al. 8-bromo-7-methoxychrysin inhibits properties of liver cancer stem cells via downregulation of beta-catenin. World J Gastroenterol. 2013;19:7680–95.

    Article  CAS  Google Scholar 

  20. Shen Q, Sun Y, Xu S. LINC01503/miR-342-3p facilitates malignancy in non-small-cell lung cancer cells via regulating LASP1. Respir Res. 2020;21:235.

    Article  CAS  Google Scholar 

  21. Wang B, Hua P, Zhang L, Li J, Zhang Y. LncRNA-IUR up-regulates PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in esophageal squamous cell carcinoma. Esophagus. 2020;17:298–304.

    Article  Google Scholar 

  22. Ji J, Wang XW. Clinical implications of cancer stem cell biology in hepatocellular carcinoma. Semin Oncol. 2012;39:461–72.

    Article  CAS  Google Scholar 

  23. Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;50:472–80.

    Article  CAS  Google Scholar 

  24. Quint K, Agaimy A, Di Fazio P, Montalbano R, Steindorf C, Jung R, et al. Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC. Virchows Arch. 2011;459:129–39.

    Article  CAS  Google Scholar 

  25. Peyrou M, Bourgoin L, Foti M. PTEN in liver diseases and cancer. World J Gastroenterol. 2010;16:4627–33.

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

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Author notes

  1. Chunlin Xu and Weiwei Sun contributed equally to this research.

Authors and Affiliations

  1. Department of Infectious Disease (No. 3), Second Affiliated Hospital of Harbin Medical University, Harbin, 150040, Heilongjiang, People’s Republic of China

    Chunlin Xu

  2. Department of Respiratory Oncology, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150040, Heilongjiang, People’s Republic of China

    Weiwei Sun, Jinglei Liu, Haihong Pu & Yinghong Li

Authors
  1. Chunlin Xu
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  2. Weiwei Sun
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Correspondence to Yinghong Li.

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Xu, C., Sun, W., Liu, J. et al. MiR-342-3p inhibits LCSC oncogenicity and cell stemness through HDAC7/PTEN axis. Inflamm. Res. 71, 107–117 (2022). https://doi.org/10.1007/s00011-021-01521-7

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  • DOI: https://doi.org/10.1007/s00011-021-01521-7

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