Evaluation of Differential Expression of MiR-18a and MiR-34a in Plasma Samples of Colorectal Cancer Patients
DOI:
https://doi.org/10.22100/jkh.v13i3.2058Keywords:
, Plasma, Colorectal cancer, miR-34a، miR-18aAbstract
Introduction: The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MiRNAs are a group of non-coding RNAs that regulate posttranscriptional expression of target genes. Dysregulation of miRNAs has been reported in associated with a variety of malignancies, including colorectal cancers. This study aimed to analyze the differential expression of miRNAs in plasma samples of colorectal cancer (CRC) patients to examine their potential value as diagnostic biomarkers.
Methods: In this case- control study, 74 plasma samples of CRC patients with stage II-IV and 36 healthy controls were collected. miR-18a, miR-34a, miR-181b and miR-146b were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase PCR (qRT-PCR). Then, statistical analyzes were performed to determine the relationship between miRNAs expression and clinical-pathological characteristics.
Results: The significantly elevated levels of miR-18a and miR-34a were detected in plasma samples compared to the healthy groups (P<0.001). ROC showed an area under the ROC curve (AUC) of 0.85 and P<0.001 for miR-18a, 0.74 and P<0.001 for miR-34a. There were no significant dysregulation of miR-146b and miR-181b between patients and controls (P>0.05).
Conclusion: Our results indicated that the expression levels of miR-18a and miR-34a are systematically elevated in CRC plasma samples. It might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and served as tumor-associated biomarkers for diagnosis.
References
Akbari A, Mobini GR, Maghsoudi R, Akhtari J, Faghihloo E, Farahnejad Z. Modulation of transforming growth factorbeta signaling transducers in colon adenocarcinoma cells induced by staphylococcal enterotoxin B. Mol Med Rep 2016;13:909-14. doi:10.3892/mmr.2015.4596
Abastabar M, Akbari A, Akhtari J, Hedayati MT, Shokohi T, Mehrad-Majd H, et al. In vitro antitumor activity of patulin on cervical and colorectal cancer cell lines. Curr Med Mycol 2017;3(1):25-9. doi:10.18869/acadpub.cmm.3.1.25
Akbari A, Ghahremani MH, Mobini GR, Abastabar M, Akhtari J, Bolhassani M, et al. Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208). Iran J Basic Med Sci 2015;18(9):856-61.
Eslamizadeh S, Heidari M, Agah S, Faghihloo E, Ghazi H, Mirzaei A, et al. The Role of MicroRNA Signature as Diagnostic Biomarkers in Different Clinical Stages of Colorectal Cancer. Cell J 2018;20(2):220-30. doi:10.22074/cellj.2018.5366
Emami SS, Akbari A, Zare AA, Agah S, Masoodi M, Talebi A, et al. MicroRNA Expression Levels and Histopathological Features of Colorectal Cancer. J Gastrointest Cancer 2018. doi:10.1007/s12029-018-0055-x
Mobini GR, Ghahremani MH, Amanpour S, Dehpour AR, Akbari A, Hoseiniharouni SM, et al. Transforming growth factor beta-induced factor 2-linked X (TGIF2LX) regulates two morphogenesis genes, Nir1 and Nir2 in human colorectal. Acta Med Iran 2016;54(5):302-7.
Agah S, Akbari A, Talebi A, Masoudi M, Sarveazad A, Mirzaei A, et al. Quantification of plasma cell-free circulating DNA at different stages of colorectal cancer. Cancer Invest 2017;35(10):625-32. doi:10.1080/07357907.2017.1408814
Fadakar P, Akbari A, Ghassemi F, Mobini GR, Mohebi M, Bolhassani M, et al. Evaluation of SD-208, a TGF-β-RI kinase inhibitor, as an anticancer agent in retinoblastoma. Acta Med Iran 2016;54(6):352-8.
Mobini GR, Ghafari A, Amanpour S, Fateh R, Ghahremani MH, Muhammadnejad S, et al. In vivo identification of novel TGIF2LX target genes in colorectal adenocarcinoma using the cDNA-AFLP method. Arab J Gastroenterol 2018;19(2):65-70. doi:10.1016/j.ajg.2018.05.001
Komatsu S, Ichikawa D, Takeshita H, Morimura R, Hirajima S, Tsujiura M, et al. Circulating miR-18a: a sensitive cancer screening biomarker in human cancer. In Vivo 2014;28(3):293-7.
Humphreys KJ, McKinnon RA, Michael MZ. miR-18a inhibits CDC42 and plays a tumour suppressor role in colorectal cancer cells. PLoS One 2014;9(11):e112288. doi:10.1371/journal.pone.0112288
Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 2007;104(39):15472-7. doi:10.1073/pnas.0707351104
Aherne ST, Madden SF, Hughes DJ, Pardini B, Naccarati A, Levy M, et al. Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression. BMC cancer 2015;15:329. doi:10.1186/s12885-015-1327-5
Vashisht A, Tanwar J, Motiani RK. Regulation of proto-oncogene Orai3 by miR18a/b and miR34a. Cell calcium 2018;75:101-11. doi:10.1016/j.ceca.2018.08.006
Bu P, Chen KY, Chen JH, Wang L, Walters J, Shin YJ, et al. A microRNA miR-34a-regulated bimodal switch targets Notch in colon cancer stem cells. Cell stem cell 2013;12(5):602-15. doi:10.1016/j.stem.2013.03.002
Corkum CP, Ings DP, Burgess C, Karwowska S, Kroll W, Michalak TI. Immune cell subsets and their gene expression profiles from human PBMC isolated by Vacutainer Cell Preparation Tube (CPT™) and standard density gradient. BMC Immunol 2015;16:48. doi:10.1186/s12865-015-0113-0
Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene 2007;26(41):6099-105. doi:10.1038/sj.onc.1210425
Akbari A, Agah S, Heidari M, Mobini GR, Faghihloo E, Sarveazad A, et al. Homeodomain protein transforming growth factor beta-induced factor 2 like, X-linked function in colon adenocarcinoma cells. Asian Pac J Cancer Prev 2017;(18):2101-8. doi:10.22034/APJCP.2017.18.8.2101
Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PloS one 2014;9(4):e92921. doi:10.1371/journal.pone.0092921
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105(30):10513-8. doi:10.1073/pnas.0804549105
Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ. Comparing the MicroRNA spectrum between serum and plasma. PloS one 2012;7(7):e41561. doi:10.1371/journal.pone.0041561
Mirzaei A, Madjd Z, Kadijani AA, Tavakoli-Yaraki M, Modarresi MH, Verdi J, et al. Evaluation of circulating cellular DCLK1 protein, as the most promising colorectal cancer stem cell marker, using immunoassay based methods. Cancer Biomarkers 2016;17(3):301-11. doi:10.3233/CBM-160642
Brunet Vega A, Pericay C, Moya I, Ferrer A, Dotor E, Pisa A, et al. microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising biomarkers. Oncol Rep 2013;30(1):320-6. doi:10.3892/or.2013.2475
Tsang WP, Kwok TT. The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras. Carcinogenesis 2009;30(6):953-9. doi:10.1093/carcin/bgp094
Matsumura T, Sugimachi K, Iinuma H, Takahashi Y, Kurashige J, Sawada G, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer 2015;113(2):275-81. doi:10.1038/bjc.2015.201
Yan LH, Chen ZN, Li L, Chen J, Mo XW, Qin YZ, et al. E2f-1 promotes DAPK2-induced anti-tumor immunity of gastric cancer cells by targeting miR-34a. Tumour Biol 2016. doi:10.1007/s13277-016-5446-7
De Antonellis P, Carotenuto M, Vandenbussche J, De Vita G, Ferrucci V, Medaglia C, et al. Early targets of miR-34a in neuroblastoma. Mol Cell Proteomics 2014;13(8):2114-31. doi:10.1074/mcp.M113.035808
Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A 2008;105(36):13421-6. doi:10.1073/pnas.0801613105
Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 2007;26(5):745-52. doi:10.1016/j.molcel.2007.05.010
Wang M, Zhang P, Li Y, Liu G, Zhou B, Zhan L, et al. The quantitative analysis by stem-loop real-time PCR revealed the microRNA-34a, microRNA-155 and microRNA-200c overexpression in human colorectal cancer. Med Oncol 2012;29(5):3113-8. doi:10.1007/s12032-012-0241-9
Agostini M, Knight RA. miR-34: from bench to bedside. Oncotarget 2014;5(4):872-81. doi:10.18632/oncotarget.1825
Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol 2014;6(3):214-30. doi:10.1093/jmcb/mju003
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