Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1

  • Original Article
  • Published:
Tumor Biology

Abstract

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence, it is imperative to determine reliable biomarkers of lung cancer prognosis. MicroRNA-490-3p has been previously reported to be a positive prognostic biomarker for hepatocellular cancer. However, its role in human lung cancer has not yet been elucidated. Here, we report that hsa-miR-490-3p expression is significantly higher in human lung cancer tissue specimens and cell line. Gain- and loss-of-function studies of hsa-miR-490-3p showed that it regulates cell proliferation and is required for induction of in vitro migration and invasion—the latter being a hallmark of epithelial to mesenchymal transition. In situ analysis revealed that hsa-miR-490-3p targets poly r(C)-binding protein 1 (PCBP1), which has been previously shown to be a negative regulator of lung cancer metastasis. Reporter assays confirmed PCBP1 as a bona fide target of miR-490-3p, and metagenomic analysis revealed an inverse relation between expression of miR-490-3p and PCBP1 in metastatic lung cancer patients. In fact, PCBP1 expression, as detected by immunohistochemistry, was undetectable in advanced stages of lung cancer patients’ brain and lymph node tissues. Xenograft tail vein colonization assays proved that high expression of miR-490-3p is a prerequisite for metastatic progression of lung cancer. Our results suggest that hsa-miR-490-3p might be a potential biomarker for lung cancer prognosis. In addition, we can also conclude that the lung cancer cells have evolved refractory mechanisms to downregulate the expression of the metastatic inhibitor, PCBP1.

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

Similar content being viewed by others

References

  1. American Cancer Society. Global Cancer Facts and Figures; 2nd Edition 2008. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-027766.pdf. Pg 15. Accessed January 19, 2016.

  2. World Health Organization. Cancer fact sheet. http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed January 18, 2016.

  3. van Zandwijk N. Neoadjuvant strategies for non-small cell lung cancer. Lung Cancer. 2001;34:s145–50.

    Article  PubMed  Google Scholar 

  4. Xiao DK, He JX. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2:154–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hu S, Wilson KD, Ghosh Z, Han L, Wang Y, Lan F, et al. MicroRNA-302 increases reprogramming efficiency via repression of NR2F2. Stem Cells (Dayton, Ohio). 2013;31:259–68.

    Article  CAS  Google Scholar 

  6. Card DA, Hebbar PB, Li L, Trotter KW, Komatsu Y, Mishina Y, et al. Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol Cell Biol. 2008;28:6426–38.

    Article  PubMed  Google Scholar 

  7. Zhang LY, Liu M, Li X, Tang H. miR-490-3p modulates cell growth and epithelial to mesenchymal transition of hepatocellular carcinoma cells by targeting endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3. J Biol Chem. 2013;288:4035–47.

    Article  CAS  PubMed  Google Scholar 

  8. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147:275–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hussey GS, Chaudhury A, Dawson AE, Lindner DJ, Knudsen CR, Wilce MC, et al. Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. Mol Cell. 2011;41:419–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chaudhury A, Hussey GS, Ray PS, Jin G, Fox PL, Howe PH. TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nat Cell Biol. 2010;12:286–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhang ZZ, Shen ZY, Shen YY, Xu J, Zhao EH, Wang M, et al. HOTAIR long noncoding RNA promotes gastric cancer metastasis through suppression of poly r(C) binding protein (PCBP) 1. Mol Cancer Ther. 2015;14(5):1162–70.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang HY, Dou KF. PCBP1 is an important mediator of TGF-β-induced epithelial to mesenchymal transition in gall bladder cancer cell line GBC-SD. Mol Biol Rep. 2014;41:5519–24.

    Article  CAS  PubMed  Google Scholar 

  13. Ghanem LR, Chatterji P, Liebhaber SA. Specific enrichment of the RNA-binding proteins PCBP1 and PCBP2 in chief cells of the murine gastric mucosa. Gene Expr Patterns. 2014;14:78–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cho SJ, Jung YS, Chen X. Poly (C)-binding protein 1 regulates p63 expression through mRNA stability. PLoS One. 2013;8(8):e71724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shi Z, Zhang T, Long W, Wang X, Zhang X, Ling X, et al. Down-regulation of poly(rC)-binding protein 1 correlates with the malignant transformation of hydatidiform moles. Int J Gynecol Cancer. 2012;22:1125–9.

    Article  PubMed  Google Scholar 

  16. Lian WX, Yin RH, Kong XZ, Zhang T, Huang XH, Zheng WW, et al. THAP11, a novel binding protein of PCBP1, negatively regulates CD44 alternative splicing and cell invasion in a human hepatoma cell line. FEBS Lett. 2012;586:1431–8.

    Article  CAS  PubMed  Google Scholar 

  17. Wang H, Vardy LA, Tan CP, Loo JM, Guo K, Li J, et al. PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase. Cancer Cell. 2010;18:52–62.

    Article  PubMed  Google Scholar 

  18. Song Q, Sheng W, Zhang X, Jiao S, F L. ILEI drives epithelial to mesenchymal transition and metastatic progression in the lung cancer cell line A549. Tumour Biol. 2014;35:1377–82.

    Article  CAS  PubMed  Google Scholar 

  19. Xue X, Wang X, Liu Y, Teng G, Wang Y, Zang X, et al. SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGFβ-mediated epithelial to mesenchymal transition in human lung cancer cell line A549. Tumour Biol. 2014;35(8):7853–9.

    Article  CAS  PubMed  Google Scholar 

  20. Hamfjord J, Stangeland AM, Hughes T, Skrede ML, Tveit KM, Ikdahl T, et al. Differential expression of miRNAs in colorectal cancer: comparison of paired tumor tissue and adjacent normal mucosa using high-throughput sequencing. PLoS One. 2012;7:e34150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nakatani F, Ferracin M, Manara MC, Ventura S, Del Monaco V, Ferrari S, et al. miR-34a predicts survival of Ewing’s sarcoma patients and directly influences cell chemo-sensitivity and malignancy. J Pathol. 2012;226:796–805.

    Article  CAS  PubMed  Google Scholar 

  22. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  23. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Can. 2006;6:259–69.

    Article  CAS  Google Scholar 

  24. Rachagani S, Macha MA, Heimann N, Seshacharyulu P, Haridas D, Chugh S, et al. Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer. Adv Drug Deliv Rev. 2015;81C:16–33.

    Article  Google Scholar 

  25. Alečković M, Kang Y. Regulation of cancer metastasis by cell-free miRNAs. Biochim Biophys Acta. 2014;1855:24–42.

    PubMed  PubMed Central  Google Scholar 

  26. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  27. Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–68.

    Article  CAS  PubMed  Google Scholar 

  28. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39:673–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, No.127, Dongming Road, Zhengzhou, Henan, 450003, China

    Jindong Li & Yongkui Yu

  2. Department of Cell Biology and Medical Genetics, Basical Medical College, Zhengzhou, Henan, 450008, China

    Qingchuan Feng

  3. Department of Thoracic Surgery, Anyang Cancer Hospital, Anyang, Henan, 455000, China

    Xudong Wei

Authors
  1. Jindong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qingchuan Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xudong Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yongkui Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jindong Li.

Ethics declarations

The study protocol was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University, China. Experiments were approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University and were performed in accordance to the “Guidelines for the Welfare of Animals in Experimental Neoplasia” published by The United Kingdom Coordinating Committee on Cancer Research.

Conflicts of interest

None.

Electronic supplementary material

ESM 1

(XLSX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Feng, Q., Wei, X. et al. MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1. Tumor Biol. 37, 15221–15228 (2016). https://doi.org/10.1007/s13277-016-5347-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5347-9

Keywords

Search

Navigation