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Tumor Biology

, Volume 36, Issue 2, pp 1313–1321 | Cite as

MicroRNA-455 inhibits proliferation and invasion of colorectal cancer by targeting RAF proto-oncogene serine/threonine-protein kinase

  • Jie Chai
  • Shan Wang
  • Dali Han
  • Wei Dong
  • Chao Xie
  • Hongliang Guo
Research Article

Abstract

Colorectal cancer (CRC, also known as colon cancer, rectal cancer, or bowel cancer) is the second leading cause of cancer mortality in the Western world. MicroRNAs (miRNAs) are a class of small (18–25 nucleotides long) noncoding RNAs with important posttranscriptional regulatory functions. miRNAs play important roles in various physiological and pathological processes including carcinogenesis in various solid cancers including CRC. In order to investigate the roles that miRNAs played in CRC, the expression of human miRNAs (in 20 normal adjacent tissue samples and 20 colon cancer samples) was examined in this study. miR-455, miR-484, and miR-101 were significantly downregulated in colon cancer samples. And overexpression of miR-455 significantly inhibited the proliferation and the invasion of SW480, but had no effect on apoptosis. PCR and Western blot showed that overexpression of miR-455 decreased protein expression of RAF proto-oncogene serine/threonine-protein kinase (RAF1) but had no effect on mRNA level. Luciferase assay indicated that miR-455 regulated RAF1 expression directly. Moreover, overexpression of RAF1 partially reversed the inhibitory effect of miR-455 on the growth and the invasion of SW480. The data indicated that miR-455 regulates the proliferation and invasion of colorectal cancer cells, at least in part, by downregulating RAF1, a direct target of miR-455. Collectively, our study demonstrated that miR-455-RAF1 may represent a new potential therapeutic target for colorectal carcinoma treatment.

Keywords

miR-455·RAF Proto-oncogene Serine/threonine-protein Kinase RAF1 Colorectal cancer Proliferation Invasion 

Notes

Acknowledgments

We thank Guangzhou Vipotion Biotechnology Co., Ltd. for the assistance in the vector construction of luciferase reporter assay.

Conflicts of interest

None

References

  1. 1.
    Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001;51:15–36.CrossRefPubMedGoogle Scholar
  2. 2.
    Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001;2:533–43.CrossRefPubMedGoogle Scholar
  3. 3.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMedGoogle Scholar
  4. 4.
    Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjot L, et al. Diagnostic and prognostic microRNAs in stage ii colon cancer. Cancer Res. 2008;68:6416–24.CrossRefPubMedGoogle Scholar
  5. 5.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMedGoogle Scholar
  6. 6.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer J Int du Cancer. 2010;127:2893–917.CrossRefGoogle Scholar
  7. 7.
    Reid JF, Sokolova V, Zoni E, Lampis A, Pizzamiglio S, Bertan C, et al. Mirna profiling in colorectal cancer highlights mir-1 involvement in met-dependent proliferation. Mol Cancer Res MCR. 2012;10:504–15.CrossRefPubMedGoogle Scholar
  8. 8.
    Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends cancer epidemiology, biomarkers & prevention. Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2010;19:1893–907.Google Scholar
  9. 9.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  10. 10.
    Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 2008;58:1284–92.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Schetter AJ, Okayama H, Harris CC. The role of microRNAs in colorectal cancer. Cancer J. 2012;18:244–52.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Michael MZ SMOC, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res: MCR. 2003;1:882–91.PubMedGoogle Scholar
  13. 13.
    Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: novel biomarker for colorectal cancer. Cancer Epidemiol Biomarkers Prev : Publ Am Assoc Cancer Res Cosponsored Am Soc of Prev Oncol. 2011;20:1272–86.CrossRefGoogle Scholar
  14. 14.
    Cummins JM, He Y, Leary RJ, Pagliarini R, Diaz Jr LA, Sjoblom T, et al. The colorectal microRNAome. Proc Natl Acad Sci U S A. 2006;103:3687–92.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA : J Am Med Assoc. 2008;299:425–36.Google Scholar
  16. 16.
    Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Mattick JS, Makunin IV: Small regulatory RNAs in mammals. Human molecular genetics 2005;14 Spec No 1:R121-132.Google Scholar
  18. 18.
    Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, et al. MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14:2690–5.CrossRefGoogle Scholar
  19. 19.
    Nagadia R, Pandit P, Coman WB, Cooper-White J, Punyadeera C. MiRNAs in head and neck cancer revisited. Cell Oncol. 2013;36:1–7.CrossRefGoogle Scholar
  20. 20.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.CrossRefPubMedGoogle Scholar
  21. 21.
    Iorio MV, Croce CM. MicroRNAs in cancer: Small molecules with a huge impact. J Clin Oncol : Off J Am Soc Clin Oncol. 2009;27:5848–56.CrossRefGoogle Scholar
  22. 22.
    Wang YW, Shi DB, Chen X, Gao C, Gao P. Clinicopathological significance of microRNA-214 in gastric cancer and its effect on cell biological behaviour. PLoS ONE. 2014;9:e91307.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Li Y, Li W, Zhang JG, Li HY, Li YM: Downregulation of tumor suppressor menin by mir-421 promotes proliferation and migration of neuroblastoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2014Google Scholar
  24. 24.
    Ma Y, She XG, Ming YZ, Wan QQ: Mir-24 promotes the proliferation and invasion of hcc cells by targeting sox7. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2014Google Scholar
  25. 25.
    Wu JH, Yao YL, Gu T, Wang ZY, Pu XY, Sun WW, et al. Mir-421 regulates apoptosis of bgc-823 gastric cancer cells by targeting caspase-3. Asian Pac J Cancer Prev : APJCP. 2014;15:5463–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Ujifuku K, Mitsutake N, Takakura S, Matsuse M, Saenko V, Suzuki K, et al. Mir-195, mir-455-3p and mir-10a (*) are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. Cancer Lett. 2010;296:241–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Hu Z, Shen WJ, Kraemer FB, Azhar S. MicroRNAs 125a and 455 repress lipoprotein-supported steroidogenesis by targeting scavenger receptor class b type i in steroidogenic cells. Mol Cell Biol. 2012;32:5035–45.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Li X, Zhang G, Luo F, Ruan J, Huang D, Feng D, et al. Identification of aberrantly expressed miRNAs in rectal cancer. Oncol Rep. 2012;28:77–84.PubMedGoogle Scholar
  29. 29.
    Swingler TE, Wheeler G, Carmont V, Elliott HR, Barter MJ, Abu-Elmagd M, et al. The expression and function of microRNAs in chondrogenesis and osteoarthritis. Arthritis Rheum. 2012;64:1909–19.CrossRefPubMedGoogle Scholar
  30. 30.
    Kyriakis JM, App H, Zhang XF, Banerjee P, Brautigan DL, Rapp UR, et al. Raf-1 activates map kinase-kinase. Nature. 1992;358:417–21.CrossRefPubMedGoogle Scholar
  31. 31.
    Brennan DF, Dar AC, Hertz NT, Chao WC, Burlingame AL, Shokat KM, et al. A raf-induced allosteric transition of ksr stimulates phosphorylation of mek. Nature. 2011;472:366–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Li P, Wood K, Mamon H, Haser W, Roberts T. Raf-1: a kinase currently without a cause but not lacking in effects. Cell. 1991;64:479–82.CrossRefPubMedGoogle Scholar
  33. 33.
    Xu ZH, Hang JB, Hu JA, Gao BL. Raf1-mek1-erk/akt axis may confer nsclc cell lines resistance to erlotinib. Int J Clin Exp Pathol. 2013;6:1493–504.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Chen L, Wang Q, Wang GD, Wang HS, Huang Y, Liu XM, et al. Mir-16 inhibits cell proliferation by targeting igf1r and the raf1-mek1/2-erk1/2 pathway in osteosarcoma. FEBS Lett. 2013;587:1366–72.CrossRefPubMedGoogle Scholar
  35. 35.
    Albers C, Illert AL, Miething C, Leischner H, Thiede M, Peschel C, et al. An RNAi-based system for loss-of-function analysis identifies raf1 as a crucial mediator of bcr-abl-driven leukemogenesis. Blood. 2011;118:2200–10.CrossRefPubMedGoogle Scholar
  36. 36.
    Kobayashi T, Aoki Y, Niihori T, Cave H, Verloes A, Okamoto N, et al. Molecular and clinical analysis of raf1 in noonan syndrome and related disorders: Dephosphorylation of serine 259 as the essential mechanism for mutant activation. Hum Mutat. 2010;31:284–94.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jie Chai
    • 1
  • Shan Wang
    • 1
  • Dali Han
    • 1
  • Wei Dong
    • 1
  • Chao Xie
    • 1
  • Hongliang Guo
    • 1
  1. 1.Department of General SurgeryShandong Cancer Hospital and InstituteJinanChina

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