Research Article

Differential Expression of miR-20a and miR-145 in Colorectal Tumors as Potential Location-specific miRNAs

Author(s): Sara Eslamizadeh, Ali-Akbar Zare, Atefeh Talebi, Seidamir Pasha Tabaeian, Zahra Shokati Eshkiki, Hafez Heydari-Zarnagh and Abolfazl Akbari*

Volume 10, Issue 1, 2021

Published on: 21 December, 2020

Page: [66 - 73] Pages: 8

DOI: 10.2174/2211536609666201221123604

Price: $65

Abstract

Background: MicroRNAs (miRNAs), as tissue specific regulators of gene transcription, may be served as biomarkers for Colorectal Cancer (CRC).

Objective: This study aimed to investigate the potential role of the cancer-related hsa-miRNAs as biomarkers in Colon Cancer (CC) and Rectal Cancer (RC).

Methods: A total of 148 CRC samples (74 rectum and 74 colon) and 74 adjacent normal tissues were collected to examine the differential expression of selected ten hsa-miRNAs using quantitative Reverse Transcriptase PCR (qRT-PCR).

Results: The significantly elevated levels of miR-21, miR-133b, miR-18a, miR-20a, and miR-135b, and decreased levels of miR-34a, miR-200c, miR-145, and let-7g were detected in colorectal tumors compared to the healthy tissues (P<0.05). Hsa-miR-20a was significantly overexpressed in rectum compared to colon (p =0.028) from a cut-off value of 3.15 with a sensitivity of 66% and a specificity of 60% and an AUC value of 0.962. Also, hsa-miR-145 was significantly overexpressed in colon compared to the rectum (p =0.02) from a cut-off value of 3.9 with a sensitivity of 55% and a specificity of 61% and an AUC value of 0.91.

Conclusion: In conclusion, hsa-miR-20a and hsa-miR-145, as potential tissue-specific biomarkers for distinguishing RC and CC, improve realizing the molecular differences between these local tumors.

Keywords: Biomarker, colon, location, microRNA, rectum, Rectal Cancer (RC).

Graphical Abstract
[1]
Akbari A, Ghahremani MH, Mobini GR, 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.
[PMID: 26523217]
[2]
Trang P, Weidhaas JB, Slack FJ. MicroRNAs and Cancer. The Molecular Basis of Human Cancer. Springer 2017; pp. 277-86.
[http://dx.doi.org/10.1007/978-1-59745-458-2_17]
[3]
Eslamizadeh S, Heidari M, Agah S, et al. The role of microRNA signature as diagnostic biomarkers in different clinical stages of colorectal cancer. Cell J 2018; 20(2): 220-30.
[http://dx.doi.org/10.22074/cellj.2018.5366] [PMID: 29633600]
[4]
Akbari A, Amanpour S, Muhammadnejad S, et al. Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma. Daru 2014; 22(1): 47.
[http://dx.doi.org/10.1186/2008-2231-22-47] [PMID: 24902843]
[5]
Mirzaei A, Madjd Z, Kadijani AA, et al. Evaluation of circulating cellular DCLK1 protein, as the most promising colorectal cancer stem cell marker, using immunoassay based methods. Cancer Biomark 2016; 17(3): 301-11.
[http://dx.doi.org/10.3233/CBM-160642] [PMID: 27802206]
[6]
Akbari A, Mobini GR, Maghsoudi R, Akhtari J, Faghihloo E, Farahnejad Z. Modulation of transforming growth factor-β signaling transducers in colon adenocarcinoma cells induced by staphylococcal enterotoxin B. Mol Med Rep 2016; 13(1): 909-14.
[http://dx.doi.org/10.3892/mmr.2015.4596] [PMID: 26647993]
[7]
Mobini GR, Ghahremani MH, Amanpour S, 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.
[PMID: 27309477]
[8]
Li JN, Zhao L, Wu J, et al. Differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer. J Dig Dis 2012; 13(1): 24-32.
[http://dx.doi.org/10.1111/j.1751-2980.2011.00551.x] [PMID: 22188913]
[9]
Akbari A, Agah S, Heidari M, 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(18): 2101-8.
[PMID: 28843229]
[10]
Marshall J, Xiu J, El-Deiry WS, et al. Comparative molecular analyses of colon versus rectal tumors. J Clin Oncol 2016; 34(Suppl 15): 3552.
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.3552]
[11]
Chen Z, Liu Z, Li W, et al. Chromosomal copy number alterations are associated with tumor response to chemoradiation in locally advanced rectal cancer. Genes Chromosomes Cancer 2011; 50(9): 689-99.
[http://dx.doi.org/10.1002/gcc.20891] [PMID: 21584903]
[12]
Sanz-Pamplona R, Cordero D, Berenguer A, et al. Gene expression differences between colon and rectum tumors. Clin Cancer Res 2011; 17(23): 7303-12.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1570] [PMID: 21976543]
[13]
Mirzaei A, Madjd Z, Kadijani AA, et al. Cancer stem cell’s potential clinical implications. Int J Cancer Manag 2017; 10: e5897.
[14]
Carethers JM. Microsatellite instability pathway and EMAST in colorectal cancer. Curr Colorectal Cancer Rep 2017; 13(1): 73-80.
[http://dx.doi.org/10.1007/s11888-017-0352-y] [PMID: 28367107]
[15]
Slattery ML, Wolff E, Hoffman MD, Pellatt DF, Milash B, Wolff RK. MicroRNAs and colon and rectal cancer: Differential expression by tumor location and subtype. Genes Chromosomes Cancer 2011; 50(3): 196-206.
[http://dx.doi.org/10.1002/gcc.20844] [PMID: 21213373]
[16]
Agostini M, Pucciarelli S, Calore F, Bedin C, Enzo M, Nitti D. miRNAs in colon and rectal cancer: A consensus for their true clinical value. Clin Chim Acta 2010; 411(17-18): 1181-6.
[http://dx.doi.org/10.1016/j.cca.2010.05.002] [PMID: 20452339]
[17]
Schee K, Boye K, Abrahamsen TW, Fodstad Ø, Flatmark K. Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer. BMC Cancer 2012; 12(1): 505.
[http://dx.doi.org/10.1186/1471-2407-12-505] [PMID: 23121918]
[18]
Emami SS, Akbari A, Zare AA, et al. MicroRNA expression levels and histopathological features of colorectal cancer. J Gastrointest Cancer 2018; 50(2): 276-84.
[http://dx.doi.org/10.1007/s12029-018-0055-x] [PMID: 29404790]
[19]
Schetter AJ, Okayama H, Harris CC. The role of microRNAs in colorectal cancer. Cancer J 2012; 18(3): 244-52.
[http://dx.doi.org/10.1097/PPO.0b013e318258b78f] [PMID: 22647361]
[20]
Ferracin M, Lupini L, Mangolini A, Negrini M. Circulating non-coding RNA as biomarkers in colorectal cancer. Adv Exp Med Biol 2016; 937: 171-81.
[http://dx.doi.org/10.1007/978-3-319-42059-2_9] [PMID: 27573900]
[21]
Agah S, Akbari A, Talebi A, et al. Quantification of plasma cell-free circulating DNA at different stages of colorectal cancer. Cancer Invest 2017; 35(10): 625-32.
[http://dx.doi.org/10.1080/07357907.2017.1408814] [PMID: 29243990]
[22]
Akbari A, Farahnejad Z, Akhtari J, Abastabar M, Mobini GR, Mehbod AS. Staphylococcus aureus enterotoxin B down-regulates the expression of Transforming Growth Factor-Beta (TGF-β) signaling transducers in human glioblastoma. Jundishapur J Microbiol 2016; 9(5): e27297.
[http://dx.doi.org/10.5812/jjm.27297] [PMID: 27540448]
[23]
Fadakar P, Akbari A, Ghassemi F, 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.
[PMID: 27306340]
[24]
Faghihloo E, Akbari A, Adjaminezhad-Fard F, Mokhtari-Azad T. Transcriptional regulation of E-cadherin and oncoprotein E7 by valproic acid in HPV positive cell lines. Iran J Basic Med Sci 2016; 19(6): 601-7.
[PMID: 27482340]
[25]
Karimi A, Majidzadeh-A K, Madjd Z, Akbari A, Habibi L, Akrami SM. Effect of copper sulfate on expression of endogenous L1 retrotransposons in HepG2 cells (Hepatocellular Carcinoma). Biol Trace Elem Res 2015; 165(2): 131-4.
[http://dx.doi.org/10.1007/s12011-015-0256-0] [PMID: 25663478]
[26]
Network CGA. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487(7407): 330-7.
[http://dx.doi.org/10.1038/nature11252] [PMID: 22810696]
[27]
Slattery ML, Pellatt DF, Mullany LE, Wolff RK, Herrick JS. Gene expression in colon cancer: A focus on tumor site and molecular phenotype. Genes Chromosomes Cancer 2015; 54(9): 527-41.
[http://dx.doi.org/10.1002/gcc.22265] [PMID: 26171582]
[28]
Minoo P, Zlobec I, Peterson M, Terracciano L, Lugli A. Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles. Int J Oncol 2010; 37(3): 707-18.
[http://dx.doi.org/10.3892/ijo_00000720] [PMID: 20664940]
[29]
Druline BR, Wang P, Bae T, et al. Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations. Sci Rep 2018; 8(1): 3161.
[30]
Lobo Prabhu KC, Vu L, Chan SK, et al. Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer. Am J Surg 2014; 207(5): 712-6.
[http://dx.doi.org/10.1016/j.amjsurg.2013.12.019] [PMID: 24791632]
[31]
Birkenkamp-Demtroder K, Olesen SH, Sørensen FB, et al. Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut 2005; 54(3): 374-84.
[http://dx.doi.org/10.1136/gut.2003.036848] [PMID: 15710986]
[32]
Missiaglia E, Jacobs B, D’Ario G, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol 2014; 25(10): 1995-2001.
[http://dx.doi.org/10.1093/annonc/mdu275] [PMID: 25057166]
[33]
Messa C, Russo F, Caruso MG, Di Leo A. EGF, TGF-alpha, and EGF-R in human colorectal adenocarcinoma. Acta Oncol 1998; 37(3): 285-9.
[http://dx.doi.org/10.1080/028418698429595] [PMID: 9677101]
[34]
Nawa T, Kato J, Kawamoto H, et al. Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology. J Gastroenterol Hepatol 2008; 23(3): 418-23.
[http://dx.doi.org/10.1111/j.1440-1746.2007.04923.x] [PMID: 17532785]
[35]
Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology 2010; 138(6): 2044-58.
[http://dx.doi.org/10.1053/j.gastro.2010.01.054] [PMID: 20420945]
[36]
Ayiomamitis GD, Notas G, Zaravinos A, et al. Differences in telomerase activity between colon and rectal cancer. Can J Surg 2014; 57(3): 199-208.
[http://dx.doi.org/10.1503/cjs.031312] [PMID: 24869613]
[37]
Liu LU, Holt PR, Krivosheyev V, Moss SF. Human right and left colon differ in epithelial cell apoptosis and in expression of Bak, a pro-apoptotic Bcl-2 homologue. Gut 1999; 45(1): 45-50.
[http://dx.doi.org/10.1136/gut.45.1.45] [PMID: 10369703]
[38]
Sommer F, Nookaew I, Sommer N, Fogelstrand P, Bäckhed F. Site-specific programming of the host epithelial transcriptome by the gut microbiota. Genome Biol 2015; 16(1): 62.
[http://dx.doi.org/10.1186/s13059-015-0614-4] [PMID: 25887251]
[39]
Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: Novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev 2011; 20(7): 1272-86.
[http://dx.doi.org/10.1158/1055-9965.EPI-11-0035] [PMID: 21551242]
[40]
Slattery ML, Herrick JS, Pellatt DF, et al. Site-specific associations between miRNA expression and survival in colorectal cancer cases. Oncotarget 2016; 7(37): 60193-205.
[http://dx.doi.org/10.18632/oncotarget.11173] [PMID: 27517623]
[41]
Omrane I, Kourda N, Stambouli N, et al. MicroRNAs 146a and 147b biomarkers for colorectal tumor’s localization. BioMed Res Int 2014; 2014: 584852.
[42]
Li X, Zhang G, Luo F, et al. Identification of aberrantly expressed miRNAs in rectal cancer. Oncol Rep 2012; 28(1): 77-84.
[PMID: 22576798]
[43]
Pekow J, Meckel K, Dougherty U, et al. Tumor suppressors miR-143 and miR-145 and predicted target proteins API5, ERK5, K-RAS, and IRS-1 are differentially expressed in proximal and distal colon. Am J Physiol Gastrointest Liver Physiol 2015; 308(3): G179-87.
[http://dx.doi.org/10.1152/ajpgi.00208.2014] [PMID: 25477374]
[44]
Zhang GJ, Li Y, Zhou H, Xiao HX, Zhou T. MiR-20a is an independent prognostic factor in colorectal cancer and is involved in cell metastasis. Mol Med Rep 2014; 10(1): 283-91.
[http://dx.doi.org/10.3892/mmr.2014.2144] [PMID: 24737193]
[45]
Cheng D, Zhao S, Tang H, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget 2016; 7(29): 45199-213.
[http://dx.doi.org/10.18632/oncotarget.9900] [PMID: 27286257]
[46]
Sokolova V, Fiorino A, Zoni E, et al. The effects of miR-20a on p21: Two mechanisms blocking growth arrest in TGF-β-responsive colon carcinoma. J Cell Physiol 2015; 230(12): 3105-14.
[http://dx.doi.org/10.1002/jcp.25051] [PMID: 26012475]
[47]
Yau TO, Wu CW, Tang CM, et al. MicroRNA-20a in human faeces as a non-invasive biomarker for colorectal cancer. Oncotarget 2016; 7(2): 1559-68.
[http://dx.doi.org/10.18632/oncotarget.6403] [PMID: 26621842]
[48]
Pellatt DF, Stevens JR, Wolff RK, et al. Expression profiles of miRNA subsets distinguish human colorectal carcinoma and normal colonic mucosa. Clin Transl Gastroenterol 2016; 7(3): e152.
[http://dx.doi.org/10.1038/ctg.2016.11] [PMID: 26963002]
[49]
Wang C-J, Zhou ZG, Wang L, et al. Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers 2009; 26(1): 27-34.
[http://dx.doi.org/10.1155/2009/921907] [PMID: 19242066]
[50]
Cui SY, Wang R, Chen LB. MicroRNA-145: A potent tumour suppressor that regulates multiple cellular pathways. J Cell Mol Med 2014; 18(10): 1913-26.
[http://dx.doi.org/10.1111/jcmm.12358] [PMID: 25124875]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy