BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma

  • Hwang, Ji-Hyun (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University) ;
  • Lee, Jungwoo (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University) ;
  • Choi, Won-Young (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University) ;
  • Kim, Min-Jung (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University) ;
  • Lee, Jiyeon (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Chu, Khanh Hoang Bao (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim, Lark Kyun (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Kim, Young-Joon (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University)
  • Received : 2022.01.04
  • Accepted : 2022.02.08
  • Published : 2022.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

Keywords

Acknowledgement

This work was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2016M3C9A4921712) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2016R1D1A1B01015292).

References

  1. European Association for the Study of the Liver (2018) EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 69, 182-236 https://doi.org/10.1016/j.jhep.2018.03.019
  2. Nio K, Yamashita T, and Kaneko S (2017) The evolving concept of liver cancer stem cells. Mol Cancer 16, 4 https://doi.org/10.1186/s12943-016-0572-9
  3. Ginestier C, Hur MH, Charafe-Jauffret E et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1, 555-567 https://doi.org/10.1016/j.stem.2007.08.014
  4. Yang L, Shi P, Zhao G et al (2020) Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther 5, 8 https://doi.org/10.1038/s41392-020-0110-5
  5. Kim WT and Ryu CJ (2017) Cancer stem cell surface markers on normal stem cells. BMB Rep 50, 285-298 https://doi.org/10.5483/BMBRep.2017.50.6.039
  6. Shi G and Jin Y (2010) Role of Oct4 in maintaining and regaining stem cell pluripotency. Stem Cell Res Ther 1, 39 https://doi.org/10.1186/scrt39
  7. Zhang H and Wang ZZ (2008) Mechanisms that mediate stem cell self-renewal and differentiation. J Cell Biochem 103, 709-718 https://doi.org/10.1002/jcb.21460
  8. Chen S, Zhu J, Wang F et al (2017) LncRNAs and their role in cancer stem cells. Oncotarget 8, 110685-110692 https://doi.org/10.18632/oncotarget.22161
  9. Fatica A and Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15, 7-21 https://doi.org/10.1038/nrg3606
  10. Statello L, Guo CJ, Chen LL, and Huarte M (2021) Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol 22, 96-118 https://doi.org/10.1038/s41580-020-00315-9
  11. Yan X, Hu Z, Feng Y et al (2015) Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell 28, 529-540 https://doi.org/10.1016/j.ccell.2015.09.006
  12. Xu Y, Yu X, Wei C, Nie F, Huang M, and Sun M (2018) Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer. J Exp Clin Cancer Res 37, 13 https://doi.org/10.1186/s13046-018-0684-8
  13. Yndestad S, Austreid E, Skaftnesmo KO, Lonning PE, and Eikesdal HP (2018) Divergent activity of the pseudogene PTENP1 in ER-positive and negative breast cancer. Mol Cancer Res 16, 78-89 https://doi.org/10.1158/1541-7786.MCR-17-0207
  14. Lou WY, Ding BS, and Fu PF (2020) Pseudogene-derived lncRNAs and their miRNA sponging mechanism in human Cancer. Front Cell Dev Biol 8, 85 https://doi.org/10.3389/fcell.2020.00085
  15. Tsui YM, Chan LK, and Ng IOL (2020) Cancer stemness in hepatocellular carcinoma: mechanisms and translational potential. Br J Cancer 122, 1428-1440 https://doi.org/10.1038/s41416-020-0823-9
  16. Zou S, Wang C, Liu J et al (2017) Sox12 is a cancer stem-like cell marker in hepatocellular carcinoma. Mol Cells 40, 847-854 https://doi.org/10.14348/MOLCELLS.2017.0129
  17. Chiba T, Miyagi S, Saraya A et al (2008) The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res 68, 7742 https://doi.org/10.1158/0008-5472.CAN-07-5882
  18. Qin XY, Suzuki H, Honda M et al (2018) Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid. Proc Natl Acad Sci U S A 115, 4969-4974 https://doi.org/10.1073/pnas.1802279115
  19. Zhang J, Luo N, Luo Y, Peng Z, Zhang T, and Li S (2012) microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb. Int J Oncol 40, 747-756 https://doi.org/10.3892/ijo.2011.1242
  20. Jia Y, Liu H, Zhuang Q et al (2012) Tumorigenicity of cancer stem-like cells derived from hepatocarcinoma is regulated by microRNA-145. Oncol Rep 27, 1865-1872 https://doi.org/10.3892/or.2012.1701
  21. Xu N, Papagiannakopoulos T, Pan G, Thomson JA, and Kosik KS (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137, 647-658 https://doi.org/10.1016/j.cell.2009.02.038
  22. Gui X, Li H, Li T, Pu H, and Lu D (2015) Long noncoding RNA CUDR regulates HULC and β-Catenin to govern human liver stem cell malignant differentiation. Mol Ther 23, 1843-1853 https://doi.org/10.1038/mt.2015.166
  23. Li H, An J, Wu M et al (2015) LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2. Oncotarget 6, 27847-27864 https://doi.org/10.18632/oncotarget.4443
  24. Lin H, Qiu X, Zhang B, and Zhang J (2018) Identification of the predictive genes for the response of colorectal cancer patients to FOLFOX therapy. OncoTargets Ther 11, 5943-5955 https://doi.org/10.2147/OTT.S167656
  25. Shi J, Levinson DF, Duan J et al (2009) Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460, 753-757 https://doi.org/10.1038/nature08192
  26. Morelli E, Gulla A, Amodio N et al (2021) CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) to explore the oncogenic lncRNA network. Methods Mol Biol 2348, 189-204 https://doi.org/10.1007/978-1-0716-1581-2_13
  27. Hon C-C, Ramilowski JA, Harshbarger J et al (2017) An atlas of human long non-coding RNAs with accurate 5' ends. Nature 543, 199-204 https://doi.org/10.1038/nature21374
  28. Lian Q, Wang S, Zhang G et al (2018) HCCDB: a database of hepatocellular carcinoma expression atlas. Genomics Proteomics Bioinformatics 16, 269-275 (Available from: http://lifeome.net/database/hccdb/download.html) https://doi.org/10.1016/j.gpb.2018.07.003
  29. Takahashi K, Tanabe K, Ohnuki M et al (2014) Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm. Nat Commun 5, 3678 https://doi.org/10.1038/ncomms4678
  30. Lamb JR, Zhang C, Xie T et al (2011) Predictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting. PLoS One 6, e20090 https://doi.org/10.1371/journal.pone.0020090
  31. Xie Z, Bailey A, Kuleshov MV et al (2021) Gene set knowledge discovery with enrichr. Curr Protoc 1, e90
  32. Chandrashekar DS, Bashel B, Balasubramanya SAH et al (2017) UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia (New York, N.Y.) 19, 649-658 https://doi.org/10.1016/j.neo.2017.05.002
  33. Lu TP, Lee CY, Tsai MH et al (2012) miRSystem: an integrated system for characterizing enriched functions and pathways of microRNA targets. PLoS One 7, e42390 https://doi.org/10.1371/journal.pone.0042390
  34. Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, and Tamayo P (2015) The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst 1, 417-425 https://doi.org/10.1016/j.cels.2015.12.004
  35. Labun K, Montague TG, Krause M, Torres Cleuren YN, Tjeldnes H, and Valen E (2019) CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Res 47, W171-W174 https://doi.org/10.1093/nar/gkz365