Skip to main content

Advertisement

SpringerLink
Log in

LncRNA LINC00470 promotes proliferation through association with NF45/NF90 complex in hepatocellular carcinoma

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

Abstract

Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play an important role in the development and progression of human cancers. LncRNA LINC00470 has been reported to function as an oncogene in glioblastoma. Until now, the roles and underlying mechanisms of LINC00470 in the progression of hepatocellular carcinoma (HCC) remain unclear. Here, we found that LINC00470 was upregulated in HCC cells and tissues. High-level LINC00470 was significantly correlated with bigger tumor size, advanced TNM stage and poor prognosis in patients with HCC. Functional studies showed that knockdown of LINC00470 expression inhibited HCC cell proliferation and cell cycle progression, while overexpression of LINC00470 showed the opposite effects. Further investigation suggested that LINC00470 was associated with NF45/NF90 complex and increased its interaction with cyclin E1 mRNA, thus inhibiting the degradation of cyclin E1 mRNA. Additionally, knockdown of cyclin E1 in LINC00470-overexpressed cells abolished its promotive effects on HCC cell proliferation. In summary, our findings suggest that targeting LINC00470 could be a potential therapeutic approach in treating HCC patients.

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

Similar content being viewed by others

Availability of data and materials

The data used in this research are available.

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21551.

    Article  PubMed  Google Scholar 

  2. Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26–46. https://doi.org/10.1016/j.cell.2013.06.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wei L, Wang X, Lv L, Zheng Y, Zhang N, Yang M. The emerging role of noncoding RNAs in colorectal cancer chemoresistance. Cell Oncol. 2019. https://doi.org/10.1007/s13402-019-00466-8.

    Article  Google Scholar 

  4. Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Can Res. 2017;77(15):3965–81. https://doi.org/10.1158/0008-5472.CAN-16-2634.

    Article  CAS  Google Scholar 

  5. Zhao J, Li L, Han ZY, Wang ZX, Qin LX. Long noncoding RNAs, emerging and versatile regulators of tumor-induced angiogenesis. Am J Cancer Res. 2019;9(7):1367–81.

    PubMed  PubMed Central  Google Scholar 

  6. Liu Y, Feng J, Sun M, Yang G, Yuan H, Wang Y, et al. Long non-coding RNA HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related hepatocellular carcinoma. Cancer Lett. 2019;454:158–70. https://doi.org/10.1016/j.canlet.2019.04.008.

    Article  CAS  PubMed  Google Scholar 

  7. Schultheiss CS, Laggai S, Czepukojc B, Hussein UK, List M, Barghash A, et al. The long non-coding RNA H19 suppresses carcinogenesis and chemoresistance in hepatocellular carcinoma. Cell Stress. 2017;1(1):37–54. https://doi.org/10.15698/cst2017.10.105.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cheng D, Deng J, Zhang B, He X, Meng Z, Li G, et al. LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation. EBioMedicine. 2018;36:159–70. https://doi.org/10.1016/j.ebiom.2018.08.055.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Pan Y, Li C, Chen J, Zhang K, Chu X, Wang R, et al. The emerging roles of long noncoding RNA ROR (lincRNA-ROR) and its possible mechanisms in human cancers. Cell Physiol Biochem. 2016;40(1–2):219–29. https://doi.org/10.1159/000452539.

    Article  CAS  PubMed  Google Scholar 

  10. Zhuang LK, Yang YT, Ma X, Han B, Wang ZS, Zhao QY, et al. MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST. Cell Death Dis. 2016;7:e2203. https://doi.org/10.1038/cddis.2016.100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25(5):666–81. https://doi.org/10.1016/j.ccr.2014.03.010.

    Article  CAS  PubMed  Google Scholar 

  12. Liu C, Zhang Y, She X, Fan L, Li P, Feng J, et al. A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy. J Hematol Oncol. 2018;11(1):77. https://doi.org/10.1186/s13045-018-0619-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu C, Fu H, Liu X, Lei Q, Zhang Y, She X, et al. LINC00470 coordinates the epigenetic regulation of ELFN2 to distract GBM cell autophagy. Mol Ther. 2018;26(9):2267–81. https://doi.org/10.1016/j.ymthe.2018.06.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lim LJ, Wong SYS, Huang F, Lim S, Chong SS, Ooi LL, et al. Roles and regulation of long noncoding RNAs in hepatocellular carcinoma. Can Res. 2019. https://doi.org/10.1158/0008-5472.CAN-19-0255.

    Article  Google Scholar 

  15. Wen X, Liu X, Mao YP, Yang XJ, Wang YQ, Zhang PP, et al. Long non-coding RNA DANCR stabilizes HIF-1alpha and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma. Theranostics. 2018;8(20):5676–89. https://doi.org/10.7150/thno.28538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang W, Xiong Z, Wei T, Li Q, Tan Y, Ling L, et al. Nuclear factor 90 promotes angiogenesis by regulating HIF-1alpha/VEGF-A expression through the PI3 K/Akt signaling pathway in human cervical cancer. Cell Death Dis. 2018;9(3):276. https://doi.org/10.1038/s41419-018-0334-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Song D, Huang H, Wang J, Zhao Y, Hu X, He F, et al. NF90 regulates PARP1 mRNA stability in hepatocellular carcinoma. Biochem Biophys Res Commun. 2017;488(1):211–7. https://doi.org/10.1016/j.bbrc.2017.05.037.

    Article  CAS  PubMed  Google Scholar 

  18. Jiang W, Huang H, Ding L, Zhu P, Saiyin H, Ji G, et al. Regulation of cell cycle of hepatocellular carcinoma by NF90 through modulation of cyclin E1 mRNA stability. Oncogene. 2015;34(34):4460–70. https://doi.org/10.1038/onc.2014.373.

    Article  CAS  PubMed  Google Scholar 

  19. Liu YR, Jiang YZ, Xu XE, Hu X, Yu KD, Shao ZM. Comprehensive transcriptome profiling reveals multigene signatures in triple-negative breast cancer. Clin Cancer Res. 2016;22(7):1653–62. https://doi.org/10.1158/1078-0432.CCR-15-1555.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang W, Wu Y, Hou B, Wang Y, Deng D, Fu Z, et al. A SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/beta-catenin pathway. Mol Oncol. 2019. https://doi.org/10.1002/1878-0261.12560.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chen Z, Yu W, Zhou Q, Zhang J, Jiang H, Hao D, et al. A novel lncRNA IHS promotes tumor proliferation and metastasis in HCC by regulating the ERK- and AKT/GSK-3beta-signaling pathways. Mol Ther Nucleic Acids. 2019;16:707–20. https://doi.org/10.1016/j.omtn.2019.04.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang X, Sun W, Shen W, Xia M, Chen C, Xiang D, et al. Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. J Hepatol. 2016;64(6):1283–94. https://doi.org/10.1016/j.jhep.2016.01.019.

    Article  CAS  PubMed  Google Scholar 

  23. Castella S, Bernard R, Corno M, Fradin A, Larcher JC. Ilf3 and NF90 functions in RNA biology. Wiley Interdiscip Rev RNA. 2015;6(2):243–56. https://doi.org/10.1002/wrna.1270.

    Article  CAS  PubMed  Google Scholar 

  24. Higuchi T, Todaka H, Sugiyama Y, Ono M, Tamaki N, Hatano E, et al. Suppression of MicroRNA-7 (miR-7) biogenesis by nuclear factor 90-nuclear factor 45 complex (NF90-NF45) controls cell proliferation in hepatocellular carcinoma. J Biol Chem. 2016;291(40):21074–84. https://doi.org/10.1074/jbc.M116.748210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhuang J, Shen L, Yang L, Huang X, Lu Q, Cui Y, et al. TGFbeta1 promotes gemcitabine resistance through regulating the LncRNA-LET/NF90/miR-145 signaling axis in bladder cancer. Theranostics. 2017;7(12):3053–67. https://doi.org/10.7150/thno.19542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, Hanchuan People’s Hospital, No. 1, Renmin Road, Hanchuan City, 432300, Hubei Province, China

    Wenwei Huang, Juntao Liu, Jijun Yan, Zhengbin Huang, Xiongjie Zhang, Yanping Mao & Xiufang Huang

Authors
  1. Wenwei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juntao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jijun Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhengbin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiongjie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yanping Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiufang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the experiments were conducted by WH, JL, JY, ZH and XZ. YM and XH designed this research and finished the manuscript.

Corresponding author

Correspondence to Xiufang Huang.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the research ethics committee of Hanchuan People’s Hospital and conducted in accordance with the Declaration of Helsinki (approval number: 2019082301). Written informed consent was obtained from all HCC patients.

Additional information

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

13577_2019_288_MOESM1_ESM.tif

Supplemental Fig. 1. Biotin RNA pull-downs were performed with cell extracts of cells using full-length LINC00470 transcript. This was followed by mass spectrometry. (TIFF 940 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, W., Liu, J., Yan, J. et al. LncRNA LINC00470 promotes proliferation through association with NF45/NF90 complex in hepatocellular carcinoma. Human Cell 33, 131–139 (2020). https://doi.org/10.1007/s13577-019-00288-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-019-00288-8

Keywords

Search

Navigation