Skip to main content

Advertisement

SpringerLink
Log in

Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

lncRNA H19 has been considered as an oncogenic lncRNA in many human tumours. In the present study, we identify the role and molecular mechanism of lncRNA H19 in melanoma.

Method

QRT-PCR was used to detect the expression of lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8), representative metabolites analysis was used to explore the biological function of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the molecular mechanism of lncRNA H19 in melanoma. We further test the function of lncRNA H19 in vivo though Xenograft tumour assay.

Results

We found that lncRNA H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and growth. We also demonstrated that lncRNA H19 may function as the sponge of miR-106a-5p to up-regulate E2F3 expression, and consequently promote the glucose metabolism and growth of melanoma.

Conclusions

This result elucidates a new mechanism for lncRNA H19 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma 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
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Arancio W, Pizzolanti G, Genovese SI, Baiamonte C, Giordano C (2014) Competing endogenous RNA and interactome bioinformatic analyses on human telomerase. Rejuvenation Res 17:161–167

    Article  CAS  PubMed  Google Scholar 

  • Berteaux N, Lottin S, Monte D, Pinte S, Quatannens B, Coll J, Hondermarck H, Curgy JJ, Dugimont T, Adriaenssens E (2005) H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J Biol Chem 280:29625–29636

    Article  CAS  PubMed  Google Scholar 

  • Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  • Hauptman N, Glavac D (2013) Long non-coding RNA in cancer. Int J Mol Sci 14:4655–4669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He QY, Wang GC, Zhang H, Tong DK, Ding C, Liu K, Ji F, Zhu X, Yang S (2016) miR-106a-5p Suppresses the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Targeting HMGA2. DNA Cell Biol 35:506–520

    Article  CAS  PubMed  Google Scholar 

  • Hombach S, Kretz M (2013) The non-coding skin: exploring the roles of long non-coding RNAs in epidermal homeostasis and disease. Bioessays 35:1093–1100

    Article  CAS  PubMed  Google Scholar 

  • Jiang YJ, Bikle DD (2014) LncRNA profiling reveals new mechanism for VDR protection against skin cancer formation. J Steroid Biochem Mol Biol 144(Pt A):87–90

    CAS  PubMed  Google Scholar 

  • Johnsson P, Ackley A, Vidarsdottir L, Lui WO, Corcoran M, Grander D, Morris KV (2013) A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol 20:440–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroemer G, Pouyssegur J (2008) Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell 13:472–482

    Article  CAS  PubMed  Google Scholar 

  • Little EG, Eide MJ (2012) Update on the current state of melanoma incidence. Dermatol Clin 30:355–361

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Chen Z, Fang J, Xu A, Zhang W, Wang Z (2016) H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation. Tumour Biol 37:263–270

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Dai C, Wu Q, Liu H, Li F (2017) Expression profiling of long noncoding RNA identifies lnc-MMP3–1 as a prognostic biomarker in external auditory canal squamous cell carcinoma. Cancer Med 6:2541–2551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luan W, Wang Y, Chen X, Shi Y, Wang J, Zhang J, Qian J, Li R, Tao T, Wei W, Hu Q, Liu N, You Y (2015) PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop. Oncotarget 6:13006–13018

    Article  PubMed  PubMed Central  Google Scholar 

  • Luan W, Li L, Shi Y, Bu X, Xia Y, Wang J, Djangmah HS, Liu X, You Y, Xu B (2016) Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22. Oncotarget 7:63901–63912

    PubMed  PubMed Central  Google Scholar 

  • Lv J, Yu YQ, Li SQ, Luo L, Wang Q (2014) Aflatoxin B1 promotes cell growth and invasion in hepatocellular carcinoma HepG2 cells through H19 and E2F1. Asian Pac J Cancer Prev 15:2565–2570

    Article  PubMed  Google Scholar 

  • Millet A, Martin AR, Ronco C, Rocchi S, Benhida R (2017) Metastatic melanoma: insights into the evolution of the treatments and future challenges. Med Res Rev 37(1):98–148

    Article  PubMed  Google Scholar 

  • Okamoto K, Morison IM, Taniguchi T, Reeve AE (1997) Epigenetic changes at the insulin-like growth factor II/H19 locus in developing kidney is an early event in Wilms tumorigenesis. Proc Natl Acad Sci USA 94:5367–5371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rachmilewitz J, Elkin M, Rosensaft J, Gelman-Kohan Z, Ariel I, Lustig O, Schneider T, Goshen R, Biran H, de Groot N et al (1995) H19 expression and tumorigenicity of choriocarcinoma derived cell lines. Oncogene 11:863–870

    CAS  PubMed  Google Scholar 

  • Schmidt K, Joyce CE, Buquicchio F, Brown A, Ritz J, Distel RJ, Yoon CH, Novina CD (2016) The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region. Cell Rep 15:2025–2037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott DA, Richardson AD, Filipp FV, Knutzen CA, Chiang GG, Ronai ZA, Osterman AL, Smith JW (2011) Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. J Biol Chem 286:42626–42634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scrable HJ, Sapienza C, Cavenee WK (1990) Genetic and epigenetic losses of heterozygosity in cancer predisposition and progression. Adv Cancer Res 54:25–62

    Article  CAS  PubMed  Google Scholar 

  • Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, Qian J, Liu N, You Y (2014) Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One 9:e86295

    Article  PubMed  PubMed Central  Google Scholar 

  • Soares MR, Huber J, Rios AF, Ramos ES (2010) Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma. Growth Horm IGF Res 20:295–297

    Article  CAS  PubMed  Google Scholar 

  • Subramanian M, Li XL, Hara T, Lal A (2015) A biochemical approach to identify direct microRNA targets. Methods Mol Biol 1206:29–37

    Article  CAS  PubMed  Google Scholar 

  • Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tech K, Deshmukh M, Gershon TR (2015) Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in medulloblastoma. Cancer Lett 356:268–272

    Article  CAS  PubMed  Google Scholar 

  • Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904–914

    Google Scholar 

  • Wang Y, Zhang Y, Yang T, Zhao W, Wang N, Li P, Zeng X, Zhang W (2017) Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144–3p in osteosarcoma cells. Oncotarget 8:59417–59434

    PubMed  PubMed Central  Google Scholar 

  • Zhang H, Chen Z, Wang X, Huang Z, He Z, Chen Y (2013) Long non-coding RNA: a new player in cancer. J Hematol Oncol 6:37

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhi F, Zhou G, Shao N, Xia X, Shi Y, Wang Q, Zhang Y, Wang R, Xue L, Wang S, Wu S, Peng Y, Yang Y (2013) miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK. PLoS One 8:e72390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by The Health and Family Planning Science and Technology Key project Foundation of Zhenjiang city (SHW2017004), The Social Development and Technology Support Foundation of Zhenjiang city (SH2011057), and The Clinical Medical Science and Technology Development Fund of Jiangsu University (JLY20160002).

Author information

Author notes

  1. Wenkang Luan, Zhou Zhou, and Xin Ni have contributed equally to this work.

Authors and Affiliations

  1. Department of Plastic Surgery, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Road, Zhenjiang, Jiangsu, China

    Wenkang Luan, Yun Xia, Jinlong Wang & Bin Xu

  2. Department of Neurosurgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

    Zhou Zhou

  3. Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

    Xin Ni

  4. Department of Respiratory Medicine, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

    Yulan Yan

Authors
  1. Wenkang Luan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhou Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jinlong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yulan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yulan Yan or Bin Xu.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 220 KB)

432_2018_2582_MOESM2_ESM.tif

Supplementary Figure 1 (A) lncRNA H19 was mainly distributed in cytoplasm analyzed by FISH. lncRNA H19 was labeled by Cy3 (red). Nucleus was stained by DAPI (blue). The tissue sections were observed in 400X magnification. The slides of cells were observed in 600X magnification. (B) The excision tumour in nude mice of A375 xenografts. (TIF 689 KB)

Supplementary material 3 (DOC 51 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luan, W., Zhou, Z., Ni, X. et al. Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis. J Cancer Res Clin Oncol 144, 531–542 (2018). https://doi.org/10.1007/s00432-018-2582-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-018-2582-z

Keywords

Search

Navigation