Frontiers of Medicine

, Volume 9, Issue 3, pp 331–343 | Cite as

MicroRNA-142-3p and microRNA-142-5p are downregulated in hepatocellular carcinoma and exhibit synergistic effects on cell motility

  • Felice Ho-Ching Tsang
  • Sandy Leung-Kuen Au
  • Lai Wei
  • Dorothy Ngo-Yin Fan
  • Joyce Man-Fong Lee
  • Carmen Chak-Lui Wong
  • Irene Oi-Lin NgEmail author
  • Chun-Ming WongEmail author
Research Article


MicroRNAs (miRNAs), an important class of small non-coding RNAs, regulate gene expression at the post-transcriptional level. miRNAs are involved in a wide range of biological processes and implicated in different diseases, including cancers. In this study, miRNA profiling and qRT-PCR validation revealed that miR-142-3p and miR-142-5p were significantly downregulated in hepatocellular carcinoma (HCC) and their expression levels decreased as the disease progressed. The ectopic expression of miR-142 significantly reduced HCC cell migration and invasion. Overexpression of either miR-142-3p or miR-142-5p suppressed HCC cell migration, and overexpression of both synergistically inhibited cell migration, which indicated that miR-142-3p and miR-142-5p may cooperatively regulate cell movement. miR-142-3p and miR-142-5p, which are mature miRNAs derived from the 3'- and 5'-strands of the precursor miR-142, target distinct pools of genes because of their different seed sequences. Pathway enrichment analysis showed a strong association of the putative gene targets of miR-142-3p and miR-142-5p with several cell motility-associated pathways, including those regulating actin cytoskeleton, adherens junctions, and focal adhesion. Importantly, a number of the putative gene targets were also significantly upregulated in human HCC cells. Moreover, overexpression of miR-142 significantly abrogated stress fiber formation in HCC cells and led to cell shrinkage. This study shows that mature miR-142 pairs collaboratively regulate different components of distinct signaling cascades and therefore affects the motility of HCC cells.


hepatocellular carcinoma microRNA metastasis cytoskeletal reorganization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

11684_2015_409_MOESM1_ESM.pdf (1.5 mb)
Supplementary material, approximately 1.46 MB.


  1. 1.
    Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 2006; 6(4): 259–269CrossRefPubMedGoogle Scholar
  2. 2.
    Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foà R, Schliwka J, Fuchs U, Novosel A, Müller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 2007; 129(7): 1401–1414PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Zhang X, Yan Z, Zhang J, Gong L, Li W, Cui J, Liu Y, Gao Z, Li J, Shen L, Lu Y. Combination of hsa-miR-375 and hsa-miR-142-5p as a predictor for recurrence risk in gastric cancer patients following surgical resection. Ann Oncol 2011; 22(10): 2257–2266CrossRefPubMedGoogle Scholar
  4. 4.
    Wu L, Cai C, Wang X, Liu M, Li X, Tang H. MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett 2011; 585(9): 1322–1330CrossRefPubMedGoogle Scholar
  5. 5.
    Shen WW, Zeng Z, Zhu WX, Fu GH. miR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med (Berl) 2013; 91(8): 989–1000CrossRefGoogle Scholar
  6. 6.
    MacKenzie TN, Mujumdar N, Banerjee S, Sangwan V, Sarver A, Vickers S, Subramanian S, Saluja AK. Triptolide induces the expression of miR-142-3p: a negative regulator of heat shock protein 70 and pancreatic cancer cell proliferation. Mol Cancer Ther 2013; 12(7): 1266–1275PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Wong CM, Kai AK, Tsang FH, Ng IO. Regulation of hepatocarcinogenesis by microRNAs. Front Biosci (Elite Ed) 2013; 5: 49–60Google Scholar
  8. 8.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120(1): 15–20CrossRefPubMedGoogle Scholar
  9. 9.
    Chen K, Rajewsky N. Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet 2006; 38(12): 1452–1456CrossRefPubMedGoogle Scholar
  10. 10.
    Maragkakis M, Alexiou P, Papadopoulos GL, Reczko M, Dalamagas T, Giannopoulos G, Goumas G, Koukis E, Kourtis K, Simossis VA, Sethupathy P, Vergoulis T, Koziris N, Sellis T, Tsanakas P, Hatzigeorgiou AG. Accurate microRNA target prediction correlates with protein repression levels. BMC Bioinformatics 2009; 10(1): 295PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Papadopoulos GL, Alexiou P, Maragkakis M, Reczko M, Hatzigeorgiou AG. DIANA-mirPath: integrating human and mouse microRNAs in pathways. Bioinformatics 2009; 25(15): 1991–1993CrossRefPubMedGoogle Scholar
  12. 12.
    Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28(1): 27–30PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Wong CM, Wong CC, Lee JM, Fan DN, Au SL, Ng IO. Sequential alterations of microRNA expression in hepatocellular carcinoma development and venous metastasis. Hepatology 2012; 55(5): 1453–1461CrossRefPubMedGoogle Scholar
  14. 14.
    Wong CC, Wong CM, Tung EK, Man K, Ng IO. Rho-kinase 2 is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion. Hepatology 2009; 49(5): 1583–1594CrossRefPubMedGoogle Scholar
  15. 15.
    Fukui K, Tamura S, Wada A, Kamada Y, Sawai Y, Imanaka K, Kudara T, Shimomura I, Hayashi N. Expression and prognostic role of RhoA GTPases in hepatocellular carcinoma. J Cancer Res Clin Oncol 2006; 132(10): 627–633CrossRefPubMedGoogle Scholar
  16. 16.
    Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell 2003; 115(2): 209–216CrossRefPubMedGoogle Scholar
  17. 17.
    Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003; 115(2): 199–208CrossRefPubMedGoogle Scholar
  18. 18.
    Ro S, Park C, Young D, Sanders KM, Yan W. Tissue-dependent paired expression of miRNAs. Nucleic Acids Res 2007; 35(17): 5944–5953PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011; 39 (Database issue): D152–D157PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Shan SW, Fang L, Shatseva T, Rutnam ZJ, Yang X, Du W, Lu WY, Xuan JW, Deng Z, Yang BB. Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci 2013; 126(Pt 6): 1517–1530CrossRefPubMedGoogle Scholar
  21. 21.
    Uchino K, Takeshita F, Takahashi RU, Kosaka N, Fujiwara K, Naruoka H, Sonoke S, Yano J, Sasaki H, Nozawa S, Yoshiike M, Kitajima K, Chikaraishi T, Ochiya T. Therapeutic effects of microRNA-582-5p and-3p on the inhibition of bladder cancer progression. Mol Ther 2013; 21(3): 610–619PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Wang F, Wang XS, Yang GH, Zhai PF, Xiao Z, Xia LY, Chen LR, Wang Y, Wang XZ, Bi LX, Liu N, Yu Y, Gao D, Huang BT, Wang J, Zhou DB, Gong JN, Zhao HL, Bi XH, Yu J, Zhang JW. miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia. Mol Biol Rep 2012; 39(3): 2713–2722CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Felice Ho-Ching Tsang
    • 1
  • Sandy Leung-Kuen Au
    • 1
  • Lai Wei
    • 1
  • Dorothy Ngo-Yin Fan
    • 1
  • Joyce Man-Fong Lee
    • 1
  • Carmen Chak-Lui Wong
    • 1
  • Irene Oi-Lin Ng
    • 1
    Email author
  • Chun-Ming Wong
    • 1
    Email author
  1. 1.State Key Laboratory for Liver Research and Department of Pathology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Personalised recommendations