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Tumor Biology

, Volume 33, Issue 5, pp 1455–1465 | Cite as

MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells

  • Qing-jun Li
  • Liang Zhou
  • Fan Yang
  • Guo-xia Wang
  • Hang Zheng
  • De-sheng Wang
  • Yong He
  • Ke-feng Dou
Research Article

Abstract

MicroRNA-10b (miR-10b) was recently reported to be dysregulated in some types of cancer and to play a role in invasion and metastasis. However, effects and potential mechanisms of action of miR-10b in the metastasis of hepatocellular carcinoma (HCC) have not been explored. In this study, we confirmed that miR-10b is highly expressed in metastatic HCC tissues and in metastatic HCC cell lines by qRT-PCR. Moreover, patients with higher miR-10b expression had significantly poorer overall survival, and high miR-10b expression was an independent predictor of poor prognosis. Inhibition of miR-10b reduced cell migration and invasion in MHCC97H cells, whereas over-expression of miR-10b in HepG2 cells increased cell migration and invasion. Bioinformatics and luciferase reporter assays revealed that miR-10b binds the 3′-UTR of CADM1 mRNA and represses its translation. Western blot and qRT-PCR showed that CADM1 is inhibited by miR-10b over-expression. Silencing of CADM1 resulted in substantially increased cell motility and invasion similar to that observed with over-expression of miR-10b in HepG2 cells. These results suggest that miR-10b may positively regulate the invasion and metastasis of HCC through targeting CADM1.

Keywords

Hepatocellular carcinoma miR-10b CADM1 Migration Invasion 

Notes

Acknowledgments

This work was supported by grants from the Major Program of the National Natural Science Foundation of China [grant no. 81030010/H0318].

Conflicts of interest

None.

References

  1. 1.
    Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Van Cutsem E, Singh H, Chow WC, Ooi LL, Chow P, Khin MW, Koo WH. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009;10:1111–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Hao K, Luk JM, Lee NP, Mao M, Zhang C, Ferguson MD, Lamb J, Dai H, Ng IO, Sham PC, Poon RT. Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters. BMC Cancer. 2009;9:389.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology. 2008;48:2047–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Griffiths-Jones S. The microRNA registry. Nucleic Acids Res. 2004;32:D109–11.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  6. 6.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferracin M, Sabbioni S, Calin GA, Grazi GL, Croce CM, Tavolari S, Chieco P, Negrini M, Bolondi L. Mir-122/cyclin g1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009;69:5761–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, Lin CD, Liao YL, Wang JL, Chau YP, Hsu MT, Hsiao M, Huang HD, Tsou AP. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49:1571–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Ji J, Zhao L, Budhu A, Forgues M, Jia HL, Qin LX, Ye QH, Yu J, Shi X, Tang ZY, Wang XW. Let-7 g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol. 2010;52:690–7.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Shimizu S, Takehara T, Hikita H, Kodama T, Miyagi T, Hosui A, Tatsumi T, Ishida H, Noda T, Nagano H, Doki Y, Mori M, Hayashi N. The let-7 family of microRNAs inhibits bcl-xl expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J Hepatol. 2010;52:698–704.CrossRefPubMedGoogle Scholar
  11. 11.
    Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Tomimaru Y, Eguchi H, Nagano H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M. MicroRNA-21 induces resistance to the anti-tumour effect of interferon-alpha/5-fluorouracil in hepatocellular carcinoma cells. Br J Cancer. 2010;103:1617–26.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gramantieri L, Fornari F, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Croce CM, Bolondi L, Negrini M. MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clin Cancer Res. 2009;15:5073–81.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pineau P, Volinia S, McJunkin K, Marchio A, Battiston C, Terris B, Mazzaferro V, Lowe SW, Croce CM, Dejean A. Mir-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci USA. 2010;107:264–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA. Therapeutic silencing of mir-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010;28:341–7.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H, Liu Z. MicroRNA-10b promotes migration and invasion through klf4 in human esophageal cancer cell lines. J Biol Chem. 2010;285:7986–94.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sasayama T, Nishihara M, Kondoh T, Hosoda K, Kohmura E. MicroRNA-10b is overexpressed in malignant glioma and associated with tumor invasive factors, uPAR and RhoC. Int J Cancer. 2009;125:1407–13.CrossRefPubMedGoogle Scholar
  19. 19.
    Nakata K, Ohuchida K, Mizumoto K, Kayashima T, Ikenaga N, Sakai H, Lin C, Fujita H, Otsuka T, Aishima S, Nagai E, Oda Y, Tanaka M. MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis. Surgery. 2011;150:916–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Li G, Wu Z, Peng Y, Liu X, Lu J, Wang L, Pan Q, He ML, Li XP. MicroRNA-10b induced by Epstein–Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells. Cancer Lett. 2010;299:29–36.CrossRefPubMedGoogle Scholar
  21. 21.
    Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S, Zucman-Rossi J. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology. 2008;47:1955–63.CrossRefPubMedGoogle Scholar
  22. 22.
    Sakurai-Yageta M, Masuda M, Tsuboi Y, Ito A, Murakami Y. Tumor suppressor CADM is involved in epithelial cell structure. Biochem Biophys Res Commun. 2009;390:977–82.CrossRefPubMedGoogle Scholar
  23. 23.
    Masuda M, Kikuchi S, Maruyama T, Sakurai-Yageta M, Williams YN, Ghosh HP, Murakami Y. Tumor suppressor in lung cancer (TSLC)1 suppresses epithelial cell scattering and tubulogenesis. J Biol Chem. 2005;280:42164–71.CrossRefPubMedGoogle Scholar
  24. 24.
    De Wever O, Pauwels P, De Craene B, Sabbah M, Emami S, Redeuilh G, Gespach C, Bracke M, Berx G. Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front. Histochem Cell Biol. 2008;130:481–94.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yang J, Weinberg RA. Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14:818–29.CrossRefPubMedGoogle Scholar
  26. 26.
    Heller G, Fong KM, Girard L, Seidl S, End-Pfutzenreuter A, Lang G, Gazdar AF, Minna JD, Zielinski CC, Zochbauer-Muller S. Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas. Oncogene. 2006;25:959–68.CrossRefPubMedGoogle Scholar
  27. 27.
    Fukuhara H, Kuramochi M, Fukami T, Kasahara K, Furuhata M, Nobukuni T, Maruyama T, Isogai K, Sekiya T, Shuin T, Kitamura T, Reeves RH, Murakami Y. Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer. Jpn J Cancer Res. 2002;93:605–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Jansen M, Fukushima N, Rosty C, Walter K, Altink R, Heek TV, Hruban R, Offerhaus JG, Goggins M. Aberrant methylation of the 5′ CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanINs. Cancer Biol Ther. 2002;1:293–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Steenbergen RD, Kramer D, Braakhuis BJ, Stern PL, Verheijen RH, Meijer CJ, Snijders PJ. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst. 2004;96:294–305.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhang W, Zhou L, Ding SM, Xie HY, Xu X, Wu J, Chen QX, Zhang F, Wei BJ, Eldin AT, Zheng SS. Aberrant methylation of the CADM1 promoter is associated with poor prognosis in hepatocellular carcinoma treated with liver transplantation. Oncol Rep. 2011;25:1053–62.PubMedGoogle Scholar
  31. 31.
    Mattila PK, Lappalainen P. Filopodia: Molecular architecture and cellular functions. Nat Rev Mol Cell Biol. 2008;9:446–54.CrossRefPubMedGoogle Scholar
  32. 32.
    Vignjevic D, Schoumacher M, Gavert N, Janssen KP, Jih G, Lae M, Louvard D, Ben-Ze'ev A, Robine S. Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Res. 2007;67:6844–53.CrossRefPubMedGoogle Scholar
  33. 33.
    Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Gabriely G, Yi M, Narayan RS, Niers JM, Wurdinger T, Imitola J, Ligon KL, Kesari S, Esau C, Stephens RM, Tannous BA, Krichevsky AM. Human glioma growth is controlled by microRNA-10b. Cancer Res. 2011;71:3563–72.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Didiano D, Hobert O. Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat Struct Mol Biol. 2006;13:849–51.CrossRefPubMedGoogle Scholar
  36. 36.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMedGoogle Scholar
  37. 37.
    Uchino K, Ito A, Wakayama T, Koma Y, Okada T, Ohbayashi C, Iseki S, Kitamura Y, Tsubota N, Okita Y, Okada M. Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung. Cancer. 2003;98:1002–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Poy MN, Hausser J, Trajkovski M, Braun M, Collins S, Rorsman P, Zavolan M, Stoffel M. Mir-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci USA. 2009;106:5813–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Qing-jun Li
    • 1
    • 2
  • Liang Zhou
    • 1
  • Fan Yang
    • 1
  • Guo-xia Wang
    • 3
  • Hang Zheng
    • 2
  • De-sheng Wang
    • 1
  • Yong He
    • 1
  • Ke-feng Dou
    • 1
  1. 1.Department of Hepatobiliary Surgery, Xijing Hospitalthe Fourth Military Medical UniversityXi’anChina
  2. 2.Department of General Surgery, the Third Affiliated HospitalXinxiang Medical UniversityXinxiangChina
  3. 3.Department of Biochemistry and Molecular Biologythe Fourth Military Medical UniversityXi’anChina

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