Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208)

Document Type: Original Article

Authors

1 Colorectal Research Center, Rasoul-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3 Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

4 Invasive Fungi Research Center, Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

5 Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

6 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

7 Experimental Medicine Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract

 
Objective(s):Transforming growth factor-β(TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC.
Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressor-miRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-∆∆CT method through student’s t-test via the GraphPad Prism software.
Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b.
Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression.

Keywords


1. Cancer Facts and Figures 2013. American Cancer Societ. Atlanta:2013.

2. Ma J, Gao HM, Hua X, Lu ZY, Gao HC. Role of TGF-β1 in human colorectal cancer and effects after cantharidinate intervention. Asian Pac J Cancer Prev 2014; 15:4045-4048.

3. Kinzler KW, Vogelstein B. Colorectal tumor, the genetic basis of human cancer. 2nd ed. New York: McGraw-Hill; 2002.p.583-612.

4. Bierie B, Moses HL. TGF-β and cancer. Cytokine Growth Factor Rev 2006; 17:29–40.

5. Jean-Jacques L. The dual role of TGF in human cancer: from tumor suppression to cancer metastasis. ISRN Mol Biol 2012; 7:1-28.

6. Akbari A, Amanpour S, Muhammadnejad S, Ghahremani MH, Gaffari SH, Dehpour AR, et al. Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma. Daru J Pharm Sci 2014; 22:47-54.

7. Yingling JM, Blanchard KL, Sawyer JS.Development of TGF-β signaling inhibitors for cancer therapy. Nat Rev Drug Discov 2004; 3:1011–1022.

8. Uhl   M, Steffen A, Jörg W, Markus W, Jing Ying Ma, Ramona A, et al. SD-208, a novel transforming growth factor-β receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in fadtro and in vivo. Cancer Res 2004; 64:7954–7961.

9. Leung SY, Niimi A, Noble A, Oates T, Williams AS, Medicherla S, et al. Effect of transforming growth factor-beta receptor I kinase inhibitor 2,4-disubstituted pteridine (SD-208) in chronic allergic airway inflammation and remodeling. J Pharmacol Exp Ther 2006; 319:586–594.

10. Ge R, Rajeev V, Ray P, Lattime E, Rittling S, Medicherla S, et al. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. Clin Cancer Res 2006; 12: 4315-4330.

11. Suzuki E, Kim S, Cheung HK, Corbley MJ, Zhang X, Sun L, et al. A novel small-molecule inhibitor of transforming growth factor β type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. Cancer Res 2007; 67:2351-2359.

12. Khalid SM, Delphine J ,Pierrick GJ, Maria N, Ryan M, Xiang HP, et al. TGF-β-RI Kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res 2011; 71:175–184.

13. Levy L, Hill CS. Alterations in components of the TGF-β superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev 2006; 17:41–58.

14. Luo K, Lodish HF. Signaling by chimeric erythropoietin-TGF-β receptors: homodimerization of the cytoplasmic domain of the type I TGF-β receptor and heterodimerization with the type II receptor are both required for intracellular signal transduction. EMBO J 1996; 15:4485–4496.

15. Subramanian G, Roderich E Schwarz, Linda H, Glenn M, Sarvajit C, Sundeep D, et al. Targeting endogenous transforming growth factor-β receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1. Cancer Res 2004; 64:5200–5211.

16. Medicherla S, Li L, Ma JY, Kapoun AM, Gaspar NJ, Liu YW, et al. Antitumor Activity of TGF-β Inhibitor is Dependent on the Microenvironment. Anticancer Res 2007; 27:4149-4158.

17. Schanen BC, Li X. Transcriptional regulation of mammalian miRNA genes. Genomics 2011; 97:1-6.

18. Jingjing L, Zhaolei Z. miRNA regulatory variation in human evolution. Review Article.  Trends Genet 2013; 29:116-124.

19.  Wan G, Mathur R, Hu X, Zhang X, Lu X. miRNA response to DNA damage. Trends Biochem Sci 2011; 36:478-484.

20. Jeanne A, Loïc de P, Alexandra HC. miRNA, Development and Disease.  Advances in Genetics. 2012. Chapter 1, Vol 80.p.1-36. 

21. Yang NQ, Zhang J, Tang QY, Guo JM, Wang GM. miRNA-1297 induces cell proliferation by targeting phosphatase and tensin homolog in testicular germ cell tumor cells. Asian Pac J Cancer Prev 2014; 15:6243-6246 .

22. Ni Y, Bin W, Zi-Fang Q, Hai-Bo P, Man-Li Z, Qi-Gui Y. The research progress of the interactions between miRNA and Wnt/beta-catenin signaling pathway in breast cancer of human and mice. Asian Pac J Cancer Prev 2014; 15:1075-1079.

23. Matthew TB, Akiko H. Regulation of miRNA biogenesis as an integrated component of growth factor signaling. Curr Opin Cell Biol 2013; 25:233-240.

24. Ruibin Z, Lijuan Q, Li J. miRNA-dependent cross-talk between VEGF and Ang-2 in hypoxia-induced microvascular dysfunction. Biochem Biophys Res Commun 2014; 23:15-19.

25. Ping L, Xiao-Bing X, Qian C, Guo-Lian P, Wan L, Jian-Cheng T, et al. MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-γ. Asian Pac J Cancer Prev 2014; 15:6949-6954.

26. Pei-Yu C, Lingfeng Q, Carmen B, Klaus C, Tai Y, Xinbo Z, et al.FGF regulates TGF-β signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression.  Cell Rep 2012; 2:1684-1696.

27. Tan JY, Marques AC. The miRNA-Mediated Cross-Talk between Transcripts Provides a Novel Layer of Posttranscriptional Regulation. Adv Genet 2014. Chapter 3. Vol 85.p. 149-199.

28. Molly H. Computational methods to identify miRNA targets. Semin Cell Dev Biol 2010; 21:738-744.

29. Zhiwei W, Yiwei Li, Dejuan K, Aamir A, Sanjeev B, Fazlul H Sarkar. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression. Cancer Lett 2010; 292:141-148.

30. Tsuchiya A, Kanno T, Nishizaki T. Adenosine exerts potent anticancer effects through diverse signaling pathways. Personalized Medicine Universe 2014; 3:35-37.

31. Floriane P, Anaïs L, Miran K, Jack RW, Claude Caron de F, Philippe M. Wnt signaling and hepatocarcinogenesis. Molecular targets for the development of innovative anticancer drugs.  J Hepatol 2013; 59:1107-1117.

32. Alberto I. MiRNA changes in chemical carcinogenesis and prevention by chemopreventive agents. Toxicol Lett 2012; 211:29-36.

33. Zhang S, Sun WY, Wu JJ, Wei W. TGF-β signaling pathway as a pharmacological target in liver diseases.  Pharmacol Res 2014; 85:15-22.

34. Sotaro K, Kousuke T, Yutaka S, Sumio S. Screening for possible miRNA–mRNA associations in a colon cancer cell line. Gene 2014; 533:520-531.

 35. Luo X,  Burwinke B, Tao S, Brenner H. MicroRNA Signatures: Novel Biomarker for Colorectal Cancer? Cancer Epidemiol Biomarkers Prev 2011; 20:1272–1286.

36. James FR, Viktorija S, Eugenio Z. miRNA Profiling in Colorectal Cancer Highlights miR-1 Involvement. Mol Cancer Res 2012; 10:504-515.

37. Ma Y, Zhang P, Yang J, Liu Z, Yang Z, Qin H. Candidate microRNA biomarkers in human colorectal cancer: systematic review profiling studies and experimental validation. Int J Cancer 2012; 130:2077-2087.

38. Tang B, He WL, Zheng C, Cheang TY, Zhang XF, Wu H, et al. Marine fungal metabolite 1386A alters the microRNA profile in MCF-7 breast cancer cells. Mol Med Rep 2011; 23:610-618.

39. Zhou J, Zhou Y, Yin B, Hao W, Zhao L, Ju W, et al. 5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro. Oncol Rep 2010; 23:121-128.

40. Nirav RS, Hexin C. MicroRNAs in pathogenesis of breast cancer: Implications in diagnosis and treatment. World J Clin Oncol 2014; 5:48–60.

41. Hironori M, Hiroshi IS, Hikaru N, Masaaki N, Takashi Y, Norio K, et al. miR-135b mediates NPM-ALK–driven oncogenicity and renders IL-17–producing immunophenotype to anaplastic large cell lymphoma. Blood 2011; 118:12-18.

42. Nagel R, le Sage C, Diosdado B, van der Waal M, Oude Vrielink JA, Bolijn A, et al. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res 2008; 68:5795-5802.

43. Fei G, Jin-lu M, Mawen-ze S, Li-ping S, Ying G. The potential clinical applications and prospects of microRNAs in lung cancer. OncoTargets Ther 2014; 7:901–906.

44. Zhu Z, Wang CP, Zhang YF, Nie L. MicroRNA-100 resensitizes resistant chondrosarcoma cells to cisplatin through direct targeting of mTOR. Asian Pac J Cancer Prev 2014; 15:917-923.