Human Cell

, Volume 33, Issue 1, pp 131–139 | Cite as

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

  • Wenwei Huang
  • Juntao Liu
  • Jijun Yan
  • Zhengbin Huang
  • Xiongjie Zhang
  • Yanping Mao
  • Xiufang HuangEmail author
Research Article


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.


Cyclin E1 mRNA stability RNA-binding protein Cell cycle 


Author contributions

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

Compliance with ethical standards

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.

Supplementary material

13577_2019_288_MOESM1_ESM.tif (941 kb)
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)


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. Scholar
  2. 2.
    Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26–46. Scholar
  3. 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. Scholar
  4. 4.
    Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Can Res. 2017;77(15):3965–81. Scholar
  5. 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.PubMedPubMedCentralGoogle Scholar
  6. 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. Scholar
  7. 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. Scholar
  8. 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. Scholar
  9. 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. Scholar
  10. 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. Scholar
  11. 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. Scholar
  12. 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. Scholar
  13. 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. Scholar
  14. 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. Scholar
  15. 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. Scholar
  16. 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. Scholar
  17. 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. Scholar
  18. 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. Scholar
  19. 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. Scholar
  20. 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. Scholar
  21. 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. Scholar
  22. 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. Scholar
  23. 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. Scholar
  24. 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. Scholar
  25. 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. Scholar

Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Wenwei Huang
    • 1
  • Juntao Liu
    • 1
  • Jijun Yan
    • 1
  • Zhengbin Huang
    • 1
  • Xiongjie Zhang
    • 1
  • Yanping Mao
    • 1
  • Xiufang Huang
    • 1
    Email author
  1. 1.Department of General SurgeryHanchuan People’s HospitalHanchuan CityChina

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