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MicroR-545 mediates colorectal cancer cells proliferation through up-regulating epidermal growth factor receptor expression in HOTAIR long non-coding RNA dependent

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Abstract

The functional impact of recently discovered miRNAs in human cancer remains to be clarified. One miRNA in colorectal cancer which has attracted attention is miR-545. In this study, we examined the function of miR-545 in proliferation of colorectal cancer cells. Expressions of HOTAIR, miRNA-545, and epidermal growth factor receptor (EGFR) mRNA were measured in 100 paired cancerous and non-cancerous tissues as well as in SW480 and LOVO colorectal cancer cell (CRC) lines by quantitative RT-PCR. The relative protein level of EGFR was measured using western blotting. Effects of miRNA-545 and HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches. Insight of mechanism of promotion cancer by miR-545 was gained from luciferase reporter assay and gene expression analysis. CRC proliferation was evaluated using clone formation and MTT assay. Differential expressions of HOTAIR, miR-545, and EGFR were observed in cancerous tissues in comparison to non-cancerous tissues. By expressional management of miR-545, we observed that miR-545 negatively regulated cell proliferation. Also luciferase reporter assay revealed that miR-545 inhibited regulated EGFR expression by affecting its 3′-UTR activity. In addition, miR-545 expression was suppressed by HOTAIR overexpression whereas enhanced by HOTAIR silence. Suppression of EGFR expression by miR-545 mimic was abrogated by HOTAIR overexpression. Monitoring of tumor growth in mice showed that miR-545 overexpression suppressed LOVO tumor growth. Our data suggested that HOTAIR long non-coding RNA mediates microR-545 regulating colorectal cancer cells proliferation.

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References

  1. Moghadamyeghaneh Z, Mills SD, Carmichael JC, Pigazzi A, Stamos MJ (2015) Risk factors of postoperative myocardial infarction after colorectal surgeries. Am Surg 81:358–364

    PubMed  Google Scholar 

  2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. doi:10.3322/caac.21262

    Article  PubMed  Google Scholar 

  3. Ohka F, Natsume A and Wakabayashi T (2012) Current trends in targeted therapies for glioblastoma multiforme. Neurol Res Int 2012:878425. doi:10.1155/2012/878425

    Article  PubMed  PubMed Central  Google Scholar 

  4. Calvert PM, Frucht H (2002) The genetics of colorectal cancer. Ann Intern Med 137:603–612

    Article  CAS  PubMed  Google Scholar 

  5. Wang J, Du Y, Liu X, Cho WC, Yang Y (2015) MicroRNAs as regulator of signaling networks in metastatic colon cancer. Biomed Res Int 2015:823620. doi:10.1155/2015/823620

    PubMed  PubMed Central  Google Scholar 

  6. He H, Zhang H, Li Z, Wang R, Li N, Zhu L (2015) miRNA-214: expression, therapeutic and diagnostic potential in cancer. Tumori 101:375–383. doi:10.5301/tj.5000318

    Article  PubMed  Google Scholar 

  7. Chawla JP, Iyer N, Soodan KS, Sharma A, Khurana SK, Priyadarshni P (2015) Role of miRNA in cancer diagnosis, prognosis, therapy and regulation of its expression by Epstein-Barr virus and human papillomaviruses: with special reference to oral cancer. Oral Oncol. doi:10.1016/j.oraloncology.2015.05.008

    PubMed  Google Scholar 

  8. Zhao Q, Li T, Qi J, Liu J, Qin C (2014) The miR-545/374a cluster encoded in the Ftx lncRNA is overexpressed in HBV-related hepatocellular carcinoma and promotes tumorigenesis and tumor progression. PLoS ONE 9:e109782. doi:10.1371/journal.pone.0109782

    Article  PubMed  PubMed Central  Google Scholar 

  9. Song B, Ji W, Guo S, Liu A, Jing W, Shao C, Li G, Jin G (2014) miR-545 inhibited pancreatic ductal adenocarcinoma growth by targeting RIG-I. FEBS Lett 588:4375–4381. doi:10.1016/j.febslet.2014.10.004

    Article  CAS  PubMed  Google Scholar 

  10. Du B, Wang Z, Zhang X, Feng S, Wang G, He J, Zhang B (2014) MicroRNA-545 suppresses cell proliferation by targeting cyclin D1 and CDK4 in lung cancer cells. PLoS ONE 9:e88022. doi:10.1371/journal.pone.0088022

    Article  PubMed  PubMed Central  Google Scholar 

  11. Valverde A, Penarando J, Canas A, Lopez-Sanchez LM, Conde F, Hernandez V, Peralbo E, Lopez-Pedrera C, de la Haba-Rodriguez J, Aranda E, Rodriguez-Ariza A (2015) Simultaneous Inhibition of EGFR/VEGFR and Cyclooxygenase-2 Targets Stemness-Related Pathways in Colorectal Cancer Cells. PLoS ONE 10:e0131363. doi:10.1371/journal.pone.0131363

    Article  PubMed  PubMed Central  Google Scholar 

  12. Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Storkel S, Schumacher KM, von Heydebreck A, Celik I, O’Byrne KJ (2012) EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13:33–42. doi:10.1016/S1470-2045(11)70318-7

    Article  CAS  PubMed  Google Scholar 

  13. Molinari F, Martin V, Saletti P, De Dosso S, Spitale A, Camponovo A, Bordoni A, Crippa S, Mazzucchelli L, Frattini M (2009) Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant. Br J Cancer 100:1087–1094. doi:10.1038/sj.bjc.6604848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S (2013) HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 32:1616–1625. doi:10.1038/onc.2012.193

    Article  CAS  PubMed  Google Scholar 

  15. Kwak SY, Kim BY, Ahn HJ, Yoo JO, Kim J, Bae IH, Han YH (2015) Ionizing radiation-inducible miR-30e promotes glioma cell invasion through EGFR stabilization by directly targeting CBL-B. FEBS J 282:1512–1525. doi:10.1111/febs.13238

    Article  CAS  PubMed  Google Scholar 

  16. Deyati A, Bagewadi S, Senger P, Hofmann-Apitius M, Novac N (2015) Systems approach for the selection of micro-RNAs as therapeutic biomarkers of anti-EGFR monoclonal antibody treatment in colorectal cancer. Sci Rep 5:8013. doi:10.1038/srep08013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bayram S, Ulger Y, Sumbul AT, Kaya BY, Rencuzogullari A, Genc A, Sevgiler Y, Bozkurt O, Rencuzogullari E (2015) A functional HOTAIR rs920778 polymorphism does not contributes to gastric cancer in a Turkish population: a case-control study. Fam Cancer. doi:10.1007/s10689-015-9813-0

    PubMed  Google Scholar 

  18. Mohamadkhani A (2014) Long noncoding RNAs in interaction with RNA binding proteins in hepatocellular carcinoma. Hepat Mon 14:e18794. doi:10.5812/hepatmon.18794

    Article  PubMed  PubMed Central  Google Scholar 

  19. 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. doi:10.1038/nature08975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xu ZY, Yu QM, Du YA, Yang LT, Dong RZ, Huang L, Yu PF, Cheng XD (2013) Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer. Int J Biol Sci 9:587–597. doi:10.7150/ijbs.6339

    Article  PubMed  PubMed Central  Google Scholar 

  21. Fu WM, Zhu X, Wang WM, Lu YF, Hu BG, Wang H, Liang WC, Wang SS, Ko CH, Waye MM, Kung HF, Li G, Zhang JF (2015) Hotair mediates hepatocarcinogenesis through suppressing MiRNA-218 expression and activating P14 and P16 signaling. J Hepatol. doi:10.1016/j.jhep.2015.05.016

    PubMed Central  Google Scholar 

  22. Jalali S, Bhartiya D, Lalwani MK, Sivasubbu S, Scaria V (2013) Systematic transcriptome wide analysis of lncRNA-miRNA interactions. PLoS ONE 8:e53823. doi:10.1371/journal.pone.0053823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Corte H, Manceau G, Blons H, Laurent-Puig P (2012) MicroRNA and colorectal cancer. Dig Liver Dis 44:195–200. doi:10.1016/j.dld.2011.10.010

    Article  CAS  PubMed  Google Scholar 

  24. Brucher BL, Jamall IS (2014) Cell-cell communication in the tumor microenvironment, carcinogenesis, and anticancer treatment. Cell Physiol Biochem 34:213–243. doi:10.1159/000362978

    Article  PubMed  Google Scholar 

  25. Poschau M, Dickreuter E, Singh-Muller J, Zscheppang K, Eke I, Liersch T, Cordes N (2015) EGFR and beta1-integrin targeting differentially affect colorectal carcinoma cell radiosensitivity and invasion. Radiother Oncol. doi:10.1016/j.radonc.2015.06.005

    PubMed  Google Scholar 

  26. Wainberg ZA and Drakaki A (2015) The importance of optimal drug sequencing in metastatic colorectal cancer: biological rationales for the observed survival benefit conferred by first-line treatment with EGFR inhibitors. Expert Opin Biol Ther:1–16. doi:10.1517/14712598.2015.1050375

    PubMed  Google Scholar 

  27. Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, Ponzetti A, Cremolini C, Amatu A, Lauricella C, Lamba S, Hobor S, Avallone A, Valtorta E, Rospo G, Medico E, Motta V, Antoniotti C, Tatangelo F, Bellosillo B, Veronese S, Budillon A, Montagut C, Racca P, Marsoni S, Falcone A, Corcoran RB, Di Nicolantonio F, Loupakis F, Siena S, Sartore-Bianchi A, Bardelli A (2015) Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med. doi:10.1038/nm.3870

    PubMed Central  Google Scholar 

  28. Yao Y, Ma J, Xue Y, Wang P, Li Z, Liu J, Chen L, Xi Z, Teng H, Wang Z, Li Z, Liu Y (2015) Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett 359:75–86. doi:10.1016/j.canlet.2014.12.051

    Article  CAS  PubMed  Google Scholar 

  29. Pilyugin M, Irminger-Finger I (2014) Long non-coding RNA and microRNAs might act in regulating the expression of BARD1 mRNAs. Int J Biochem Cell Biol 54:356–367. doi:10.1016/j.biocel.2014.06.018

    Article  CAS  PubMed  Google Scholar 

  30. Yao Y, Ma J, Xue Y, Wang P, Li Z, Liu J, Chen L, Xi Z, Teng H, Wang Z (2015) Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett 359:75–86

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Key Laboratory of Living Donor Liver Transplantation, Center of Liver Transplantation, Ministry of Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China

    Xinli Huang & Sen Lu

  2. Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd., Nanjing, 210029, People’s Republic of China

    Sen Lu

Authors
  1. Xinli Huang
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  2. Sen Lu
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Correspondence to Sen Lu.

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The authors declare that they have no competing interests.

Funding

This study was supported by CSCO-Merck Serono Oncology Research Fund (SCORE) (grant number Y-MX2015-094).

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Huang, X., Lu, S. MicroR-545 mediates colorectal cancer cells proliferation through up-regulating epidermal growth factor receptor expression in HOTAIR long non-coding RNA dependent. Mol Cell Biochem 431, 45–54 (2017). https://doi.org/10.1007/s11010-017-2974-4

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  • DOI: https://doi.org/10.1007/s11010-017-2974-4

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