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Let-7b inhibits cell proliferation, migration, and invasion through targeting Cthrc1 in gastric cancer

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Tumor Biology

Abstract

Dysregulation of specific microRNAs (miRNAs) is found to play a vital role in carcinogenesis and progression of gastric cancer (GC). In the present study, we investigated the expression profiles of miRNAs in gastric cancer. Let-7b was found downregulated remarkably in gastric cancer tissues and was correlated with Helicobacter pylori infection, tumor stage, and lymphatic metastasis. Ectopic expression of let-7b suppressed the growth, migration, invasion, and tumorigenicity of GC cells, whereas let-7b knockdown promoted these phenotypes. Bioinformatic analysis predicted collagen triple helix repeat containing 1 (Cthrc1) as a direct target of let-7b. Luciferase assay showed that let-7b repressed the activity of Cthrc1 through binding its 3’UTR. Western blotting also confirmed that the protein levels of Cthrc1 were decreased by let-7b. Cthrc1 was significantly upregulated and reversely correlated with let-7b levels in GC. Co-expression of let-7b and Cthrc1 without its 3’UTR could rescue cell growth, migration, and invasion inhibited by let-7b. These results suggest that let-7b may directly target Cthrc1 and function as a tumor suppressor gene in GC.

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References

  1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  2. Zeng H, Zheng R, Guo Y, et al. Cancer survival in China, 2003–2005: a population-based study. Int J Cancer. 2014. doi:10.1002/ijc.29227.

    PubMed Central  Google Scholar 

  3. Sheridan C. Gene therapy finds its niche. 2011;29:121–8.

  4. D’Angelo G, Di Rienzo T, Ojetti V. Microarray analysis in gastric cancer: a review. World J Gastroenterol. 2014;20:11972–6.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Garajová I, Le Large TY, Frampton AE, et al. Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer. Biomed Res Int. 2014;2014:678401.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wang H, Yuan X, Zhou Z, et al. MicroRNAs might be promising biomarkers of human gliomas. Asian Pac J Cancer Prev. 2011;12:833–5.

    PubMed  Google Scholar 

  7. Xiao L, Wang JY. RNA-binding proteins and microRNAs in gastrointestinal epithelial homeostasis and diseases. Curr Opin Pharmacol. 2014;19C:46–53.

    Article  Google Scholar 

  8. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901–6.

    Article  CAS  PubMed  Google Scholar 

  9. Ruby JG, Jan C, Player C, et al. Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell. 2006;127:1193–207.

    Article  CAS  PubMed  Google Scholar 

  10. Lawrie CH, Chi J, Taylor S, et al. Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma. J Cell Mol Med. 2009;13:1248–60.

    Article  CAS  PubMed  Google Scholar 

  11. Xiang KM, Li XR. MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal cancer cells. Asian Pac J Cancer Prev. 2014;15:3767–72.

    Article  PubMed  Google Scholar 

  12. Song CQ, Zhang JH, Shi JC, et al. Bioinformatic prediction of SNPs within miRNA binding sites of inflammatory genes associated with gastric cancer. Asian Pac J Cancer Prev. 2014;15:937–43.

    Article  PubMed  Google Scholar 

  13. Sharma SB, Lin CC, Farrugia MK, et al. microRNAs-206 and -21 cooperate to promote RAS-ERK signaling by suppressing the translation of RASA1 and SPRED1. Mol Cell Biol. 2014

  14. Tahara T, Okubo M, Shibata T, et al. Association between common genetic variants in pre-microRNAs and prognosis of advanced gastric cancer treated with chemotherapy. Anticancer Res. 2014;34:5199–204.

    PubMed  Google Scholar 

  15. Martínez-Pacheco M, Hidalgo-Miranda A, Romero-Córdoba S, et al. MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects. Gene. 2014;533:508–14.

    Article  PubMed  Google Scholar 

  16. Qin S, Ai F, Ji WF, et al. miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer. Asian Pac J Cancer Prev. 2013;14:835–40.

    Article  PubMed  Google Scholar 

  17. Xu L, Dai WQ, Xu XF, et al. Effects of multiple-target anti-microRNA antisense oligodeoxyribonucleotides on proliferation and migration of gastric cancer cells. Asian Pac J Cancer Prev. 2012;13:3203–7.

    Article  PubMed  Google Scholar 

  18. Tong F, Cao P, Yin Y, et al. MicroRNAs in gastric cancer: from benchtop to bedside. Dig Dis Sci. 2014;59:24–30.

    Article  CAS  PubMed  Google Scholar 

  19. González CA, Sala N, Rokkas T. Gastric cancer: epidemiologic aspects. Helicobacter. 2013;18:34–8.

    Article  PubMed  Google Scholar 

  20. Wang JL, Hu Y, Kong X, et al. Candidate microRNA biomarkers in human gastric cancer: a systematic review and validation study. PLoS One. 2013;8:e73683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shimizu S, Takehara T, Hikita H, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  22. Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A. 2008;105:3903–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  24. Pasquinelli AE, Reinhart BJ, Slack F, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000;408:86–9.

    Article  CAS  PubMed  Google Scholar 

  25. Kim HC, Kim YS, Oh HW, et al. Collagen triple helix repeat containing 1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells. Oncotarget. 2014;5:519–29.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gu L, Liu L, Zhong L, et al. Cthrc1 overexpression is an independent prognostic marker in gastric cancer. Hum Pathol. 2014;45:1031–8.

    Article  CAS  PubMed  Google Scholar 

  27. Pyagay P, Heroult M, Wang Q, et al. Collagen triple helix repeat containing 1, a novel secreted protein in injured and diseased arteries, inhibits collagen expression and promotes cell migration. Circ Res. 2005;96:261–8.

    Article  CAS  PubMed  Google Scholar 

  28. Tang L, Dai DL, Su M, et al. Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers. Clin Cancer Res. 2006;12:3716–22.

    Article  CAS  PubMed  Google Scholar 

  29. Park EH, Kim S, Jo JY, et al. Collagen triple helix repeat containing-1 promotes pancreatic cancer progression by regulating migration and adhesion of tumor cells. Carcinogenesis. 2013;34:694–702.

    Article  CAS  PubMed  Google Scholar 

  30. Palma M, Lopez L, García M, et al. Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer. BMC Clin Pathol. 2012;12:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kharaishvili G, Cizkova M, Bouchalova K, et al. Collagen triple helix repeat containing 1 protein, periostin and versican in primary and metastatic breast cancer: an immunohistochemical study. J Clin Pathol. 2011;64:977–82.

    Article  PubMed  Google Scholar 

  32. Tan F, Liu F, Liu H, et al. CTHRC1 is associated with peritoneal carcinomatosis in colorectal cancer: a new predictor for prognosis. Med Oncol. 2013;30:473.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.812111519 and No.81272712) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801).

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Authors and Affiliations

  1. Department of General Surgery, the Affiliated Hospital of Nantong University, Nantong, China

    Junbo Yu

  2. Department of General Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China

    Jin Feng & Yong Xu

  3. Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Xiaofei Zhi, Jie Tang, Li Yang & Zekuan Xu

  4. Department of General Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

    Zenliang Li

  5. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China

    Zhibin Hu

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  1. Junbo Yu
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  2. Jin Feng
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  3. Xiaofei Zhi
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  4. Jie Tang
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  5. Zenliang Li
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  6. Yong Xu
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  7. Li Yang
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  8. Zhibin Hu
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  9. Zekuan Xu
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Corresponding author

Correspondence to Zekuan Xu.

Additional information

Junbo Yu and Jin Feng contributed equally to this work.

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Yu, J., Feng, J., Zhi, X. et al. Let-7b inhibits cell proliferation, migration, and invasion through targeting Cthrc1 in gastric cancer. Tumor Biol. 36, 3221–3229 (2015). https://doi.org/10.1007/s13277-014-2950-5

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  • DOI: https://doi.org/10.1007/s13277-014-2950-5

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