The Effect of Simultaneous Expression of miR-146a-5p and miR-193a-5p on the Expression of MMP-9 Gene in Colorectal Cancer (HT-29 cell line)

Saeed Noorolyai, Ahad Mokhtarzadeh

Abstract


Background and Purpose: Colorectal cancer is the third leading cause of cancer death in the worldwide. microRNAs are a group of non-coding small RNAs that inhibit target mRNA translation. miR-146a-5p and miR-193a-5p are known as tumor-suppressors, which down expressed in many cancers. In this study, the purpose was to restore the expression level of miR-146a-5p and miR-193a-5p up to normal level, and to investigate their synergetic effects on MMP-9 gene expression in HT-29 cells. Materials and Methods: The HT-29 cell line from colorectal cancer was cultured in RPMI-1640 culture media. Then, miR-146a and miR-193a were transfected with Jet-PEI reagent.The expression of miR-146a, miR-193a and MMP-9 gene in transfected HT-29 cells and control cells were evaluated by using the qR-PCR technique. Statistical analyzes were performed using GraphPad Prism 6 statistical software. Results: Our results show that the expression levels of miR-193a and miR-146a were increased after transfection, and in comparison with un-transfected cells, the expression level of MMP-9 was decreased. Conclusion: The results of this study showed that the simultaneous replacement of miR-146a and miR-193a may act as a potent tumor-suppressor and has an important role in cancer cell migration by influencing molecules such as MMP-9. Thus, simultaneous use of these two microRNAs may be suggested as a potential therapeutic goal in the treatment of colorectal cancer.

Keywords


Colorectal Cancer, HT-29, miR-146a-5p, miR-193a-5p, MMP-9

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References


Blanco-Calvo M, Concha Á, Figueroa A, Garrido F, Valladares-Ayerbes M. Colorectal cancer classification and cell heterogeneity: a systems oncology approach. International journal of molecular sciences. 2015;16(6):13610-32.

Haraldsdottir S, Einarsdottir HM, Smaradottir A, Gunnlaugsson A, Halfdanarson T. Colorectal cancer-review. Laeknabladid. 2014;100(2):75-82.

Geramizadeh B. Molecular biomarkers of colorectal cancer: A Review of Published Articles from Iran. Annals of colorectal research. 2015;3(3).

Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar M, Mulrow C, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997;112(2):594-642.

Almeida MI, Reis RM, Calin GA. MicroRNA history: discovery, recent applications, and next frontiers. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2011;717(1):1-8.

Ma L, Bajic VB, Zhang Z. On the classification of long non-coding RNAs. RNA biology. 2013;10(6):924-33.

Mohammadi A, Mansoori B, Baradaran B. The role of microRNAs in colorectal cancer. Biomedicine & Pharmacotherapy. 2016;84:705-13.

Calin GA, Croce CM. MicroRNA signatures in human cancers. Nature reviews cancer. 2006;6(11):857.

Baghbani E, Khaze V, Sadreddini S, Mokhtarzadeh A, Mansoori B, Mohammadi A, et al. PTPN22 Silencing in Human Acute T-Cell Leukemia Cell Line (Jurkat Cell) and its Effect on the Expression of miR-181a and miR-181b. Advanced Pharmaceutical Bulletin. 2018;8(2):277.

Henry JC, Azevedo-Pouly ACP, Schmittgen TD. MicroRNA replacement therapy for cancer. Pharmaceutical research. 2011;28(12):3030-42.

Bader AG, Brown D, Winkler M. The promise of microRNA replacement therapy. Cancer research. 2010;70(18):7027-30.

Hosseinahli N, Aghapour M, Duijf PH, Baradaran B. Treating cancer with microRNA replacement therapy: A literature review. Journal of cellular physiology. 2018;233(8):5574-88.

Kent O, Mendell J. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene. 2006;25(46):6188.

Parasramka MA, Ho E, Williams DE, Dashwood RH. MicroRNAs, diet, and cancer: new mechanistic insights on the epigenetic actions of phytochemicals. Molecular carcinogenesis. 2012;51(3):213-30.

Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends in molecular medicine. 2014;20(8):460-9.

Bader A, Brown D, Stoudemire J, Lammers P. Developing therapeutic microRNAs for cancer. Gene therapy. 2011;18(12):1121.

Li L, Chen XP, Li YJ. MicroRNA‐146a and human disease. Scandinavian journal of immunology. 2010;71(4):227-31.

Iborra M, Bernuzzi F, Invernizzi P, Danese S. MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmunity reviews. 2012;11(5):305-14.

Wuchty S, Arjona D, Bozdag S, Bauer PO. Involvement of microRNA families in cancer. Nucleic acids research. 2012;40(17):8219-26.

Gambari R, Brognara E, Spandidos DA, Fabbri E. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: Νew trends in the development of miRNA therapeutic strategies in oncology. International journal of oncology. 2016;49(1):5-32.

Li H, Xie S, Liu M, Chen Z, Liu X, Wang L, et al. The clinical significance of downregulation of mir-124-3p, mir-146a-5p, mir-155-5p and mir-335-5p in gastric cancer tumorigenesis. International journal of oncology. 2014;45(1):197-208.

Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. International journal of cancer. 2010;127(1):118-26.

Suzuki H, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, et al. Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer. Cancer research. 2011.

Mack GS. MicroRNA gets down to business. Nature biotechnology. 2007;25(6):631.

Naidu S, Magee P, Garofalo M. MiRNA-based therapeutic intervention of cancer. Journal of hematology & oncology. 2015;8(1):68.

Orellana EA, Kasinski AL. MicroRNAs in cancer: a historical perspective on the path from discovery to therapy. Cancers. 2015;7(3):1388-405.

Zeng ZS, Huang Y, Cohen AM, Guillem JG. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. Journal of clinical oncology. 1996;14(12):3133-40.

Zeng Z, Guillem J. Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastases. British journal of cancer. 1995;72(3):575.

Liang S, Chang L. Serum matrix metalloproteinase-9 level as a biomarker for colorectal cancer: a diagnostic meta-analysis. Biomarkers in medicine. 2018;12(4):393-402.

Hu Y, Ou Y, Wu K, Chen Y, Sun W. miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway. Tumor Biology. 2012;33(6):1863-70.




DOI: https://doi.org/10.7575/aiac.abcmed.v.7n.2p.7

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