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Erschienen in: Tumor Biology 12/2015

01.12.2015 | Research Article

MicroRNA 211 expression is upregulated and associated with poor prognosis in colorectal cancer: a case–control study

verfasst von: Ahmet Taner Sümbül, Bülent Göğebakan, Süleyman Bayram, Celal Yücel Batmacı, Serdar Öztuzcu

Erschienen in: Tumor Biology | Ausgabe 12/2015

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Abstract

Increasingly more evidence support the role of the microRNAs (miRNA) in tumorigenesis. The role of up/downregulation microRNA-211 (miR-211) during human tumorigenesis is still contentious and may exhibit tissue-specific regulatory manner, but the exhaustive mechanisms underlying its pro/anti-oncogenic effects remain to be unknown. Sixty-six patients that were diagnosed and operated with colorectal cancer (CRC) and sixty-five healthy cases that were age and sex compatible with them were included in our study. miRNA was isolated from the formalin-fixed paraffin-embedded (FFPE) tissues of all cases. The expression level of miR-211 in matched normal and tumor tissues of CRC group and healthy group was evaluated using a quantitative real-time RT-PCR (qRT-PCR). Based on the average miR-211 levels, two groups of low or high expression were formed in CRC group. Correlation of the patients’ clinicopathological factors and survival was also analyzed. No statistically significant differences were found in miR-211 levels among tumorous and normal tissues of CRC patient group (P = 0.59). Also, no statistically significant correlation was determined between clinicopathological factors and miR-211 expression level in CRC group. However, miR-211 expression levels between the CRC group and the healthy group were determined to be of statistical significance (P < 0.0001). There were 33 (50 %) CRC patients that expressed low levels of miR-211 and 33 (50 %) CRC patients that expressed high levels of miR-211. A median survival between low levels of miR-211 group and high levels of miR-211 group was evaluated via Kaplan–Meier, and the difference was of statistical significance (P = 0.035). The univariate analysis of the factors that may affect survival indicated invasion depth (P = 0.063), lymphovascular invasion (P = 0.011), perineural invasion (P = 0.009), and miR-211 expression level (P = 0.041) presence to be effective. In the multivariate analysis of these factors with overall survival, only miR-211 expression level (P = 0.01) was effective on overall survival. Our results suggest for the first time that miR-211 expressed more in CRC patients than in healthy group could be a new prognostic biomarker in order to predict survival. Independent studies are needed to validate our findings in a larger series, as well as in cancer of different tissues.
Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014. doi:10.1002/ijc.29210.PubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014. doi:10.​1002/​ijc.​29210.PubMed
2.
Zurück zum Zitat Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5.CrossRefPubMed Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5.CrossRefPubMed
3.
Zurück zum Zitat Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X, et al. Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2013;6(12):2904–11.PubMedPubMedCentral Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X, et al. Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2013;6(12):2904–11.PubMedPubMedCentral
4.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRefPubMed Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRefPubMed
5.
Zurück zum Zitat Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRefPubMed Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRefPubMed
6.
Zurück zum Zitat Waldman SA, Terzic A. Translating MicroRNA discovery into clinical biomarkers in cancer. JAMA. 2007;297(17):1923–5.CrossRefPubMed Waldman SA, Terzic A. Translating MicroRNA discovery into clinical biomarkers in cancer. JAMA. 2007;297(17):1923–5.CrossRefPubMed
7.
Zurück zum Zitat Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.CrossRefPubMed Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.CrossRefPubMed
8.
Zurück zum Zitat Sümbül AT, Göğebakan B, Ergün S, Yengil E, Batmacı CY, Tonyalı O, et al. miR-204-5p expression in colorectal cancer: an autophagy-associated gene. Tumour Biol. 2014. doi:10.1007/s13277-014-2596-3.PubMed Sümbül AT, Göğebakan B, Ergün S, Yengil E, Batmacı CY, Tonyalı O, et al. miR-204-5p expression in colorectal cancer: an autophagy-associated gene. Tumour Biol. 2014. doi:10.​1007/​s13277-014-2596-3.PubMed
9.
Zurück zum Zitat Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127(1):118–26.CrossRefPubMed Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127(1):118–26.CrossRefPubMed
10.
Zurück zum Zitat Chang KW, Liu CJ, Chu TH, Cheng HW, Hung PS, Hu WY, et al. Association between high miR-211 microRNA expression and the poor prognosis of oral carcinoma. J Dent Res. 2008;87(11):1063–8.CrossRefPubMed Chang KW, Liu CJ, Chu TH, Cheng HW, Hung PS, Hu WY, et al. Association between high miR-211 microRNA expression and the poor prognosis of oral carcinoma. J Dent Res. 2008;87(11):1063–8.CrossRefPubMed
11.
Zurück zum Zitat Cai C, Ashktorab H, Pang X, Zhao Y, Sha W, Liu Y, et al. MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5. PLoS One. 2012;7(1), e29750.CrossRefPubMedPubMedCentral Cai C, Ashktorab H, Pang X, Zhao Y, Sha W, Liu Y, et al. MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5. PLoS One. 2012;7(1), e29750.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Chu TH, Yang CC, Liu CJ, Lui MT, Lin SC, Chang KW. miR-211 promotes the progression of head and neck carcinomas by targeting TGFβRII. Cancer Lett. 2013;337(1):115–24.CrossRefPubMed Chu TH, Yang CC, Liu CJ, Lui MT, Lin SC, Chang KW. miR-211 promotes the progression of head and neck carcinomas by targeting TGFβRII. Cancer Lett. 2013;337(1):115–24.CrossRefPubMed
13.
Zurück zum Zitat Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, et al. Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol Cell. 2010;40(5):841–9.CrossRefPubMedPubMedCentral Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, et al. Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol Cell. 2010;40(5):841–9.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Mazar J, DeYoung K, Khaitan D, Meister E, Almodovar A, Goydos J, et al. The regulation of miRNA-211 expression and its role in melanoma cell invasiveness. PLoS One. 2010;5(11), e13779.CrossRefPubMedPubMedCentral Mazar J, DeYoung K, Khaitan D, Meister E, Almodovar A, Goydos J, et al. The regulation of miRNA-211 expression and its role in melanoma cell invasiveness. PLoS One. 2010;5(11), e13779.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Sakurai E, Maesawa C, Shibazaki M, Yasuhira S, Oikawa H, Sato M, et al. Downregulation of microRNA-211 is involved in expression of preferentially expressed antigen of melanoma in melanoma cells. Int J Oncol. 2011;39(3):665–72.PubMed Sakurai E, Maesawa C, Shibazaki M, Yasuhira S, Oikawa H, Sato M, et al. Downregulation of microRNA-211 is involved in expression of preferentially expressed antigen of melanoma in melanoma cells. Int J Oncol. 2011;39(3):665–72.PubMed
16.
Zurück zum Zitat Boyle GM, Woods SL, Bonazzi VF, Stark MS, Hacker E, Aoude LG, et al. Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor. Pigment Cell Melanoma Res. 2011;24(3):525–37.CrossRefPubMed Boyle GM, Woods SL, Bonazzi VF, Stark MS, Hacker E, Aoude LG, et al. Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor. Pigment Cell Melanoma Res. 2011;24(3):525–37.CrossRefPubMed
17.
Zurück zum Zitat Xu Y, Brenn T, Brown ER, Doherty V, Melton DW. Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors. Br J Cancer. 2012;106(3):553–61.CrossRefPubMedPubMedCentral Xu Y, Brenn T, Brown ER, Doherty V, Melton DW. Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors. Br J Cancer. 2012;106(3):553–61.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Giovannetti E, van der Velde A, Funel N, Vasile E, Perrone V, Leon LG, et al. High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer. PLoS One. 2012;7(11), e49145.CrossRefPubMedPubMedCentral Giovannetti E, van der Velde A, Funel N, Vasile E, Perrone V, Leon LG, et al. High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer. PLoS One. 2012;7(11), e49145.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Maftouh M, Avan A, Funel N, Frampton AE, Fiuji H, Pelliccioni S, et al. miR-211 modulates gemcitabine activity through downregulation of ribonucleotide reductase and inhibits the invasive behavior of pancreatic cancer cells. Nucleosides Nucleotides Nucleic Acids. 2014;33(4–6):384–93.CrossRefPubMed Maftouh M, Avan A, Funel N, Frampton AE, Fiuji H, Pelliccioni S, et al. miR-211 modulates gemcitabine activity through downregulation of ribonucleotide reductase and inhibits the invasive behavior of pancreatic cancer cells. Nucleosides Nucleotides Nucleic Acids. 2014;33(4–6):384–93.CrossRefPubMed
20.
Zurück zum Zitat Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a evelopmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113(1):25–36.CrossRefPubMed Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a evelopmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113(1):25–36.CrossRefPubMed
21.
Zurück zum Zitat Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432(7014):226–30.CrossRefPubMed Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432(7014):226–30.CrossRefPubMed
22.
Zurück zum Zitat Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, et al. Regulation of the germinal center response by microRNA-155. Science. 2007;316(5824):604–8.CrossRefPubMed Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, et al. Regulation of the germinal center response by microRNA-155. Science. 2007;316(5824):604–8.CrossRefPubMed
24.
Zurück zum Zitat Liu H, Du L, Wen Z, Yang Y, Li J, Wang L, et al. Up-regulation of miR-182 expression in colorectal cancer tissues and its prognostic value. Int J Colorectal Dis. 2013;28(5):697–703.CrossRefPubMed Liu H, Du L, Wen Z, Yang Y, Li J, Wang L, et al. Up-regulation of miR-182 expression in colorectal cancer tissues and its prognostic value. Int J Colorectal Dis. 2013;28(5):697–703.CrossRefPubMed
25.
Zurück zum Zitat Zhang G, Xia S, Tian H, Liu Z, Zhou T. Clinical significance of miR-22 expression in patients with colorectal cancer. Med Oncol. 2012;29(5):3108–12.CrossRefPubMed Zhang G, Xia S, Tian H, Liu Z, Zhou T. Clinical significance of miR-22 expression in patients with colorectal cancer. Med Oncol. 2012;29(5):3108–12.CrossRefPubMed
26.
Zurück zum Zitat Wang CJ, Zhou ZG, Wang L, Yang L, Zhou B, Gu J, et al. Clinicopathological significance of microRNA-31, −143 and −145 expression in colorectal cancer. Dis Markers. 2009;26(1):27–34.CrossRefPubMedPubMedCentral Wang CJ, Zhou ZG, Wang L, Yang L, Zhou B, Gu J, et al. Clinicopathological significance of microRNA-31, −143 and −145 expression in colorectal cancer. Dis Markers. 2009;26(1):27–34.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Zhou T, Zhang G, Liu Z, Xia S, Tian H. Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer. Int J Colorectal Dis. 2013;28(1):19–24.CrossRefPubMed Zhou T, Zhang G, Liu Z, Xia S, Tian H. Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer. Int J Colorectal Dis. 2013;28(1):19–24.CrossRefPubMed
28.
Zurück zum Zitat Zhou T, Zhang GJ, Zhou H, Xiao HX, Li Y. Overexpression of microRNA-183 in human colorectal cancer and its clinical significance. Eur J Gastroenterol Hepatol. 2014;26(2):229–33.CrossRefPubMed Zhou T, Zhang GJ, Zhou H, Xiao HX, Li Y. Overexpression of microRNA-183 in human colorectal cancer and its clinical significance. Eur J Gastroenterol Hepatol. 2014;26(2):229–33.CrossRefPubMed
29.
Zurück zum Zitat Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR, et al. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2014;259(4):735–43.CrossRefPubMedPubMedCentral Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR, et al. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2014;259(4):735–43.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X, et al. Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2013;6(12):2904–11.PubMedPubMedCentral Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X, et al. Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2013;6(12):2904–11.PubMedPubMedCentral
31.
Zurück zum Zitat Sarver AL, Li L, Subramanian S. MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res. 2010;70:9570–80.CrossRefPubMed Sarver AL, Li L, Subramanian S. MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res. 2010;70:9570–80.CrossRefPubMed
32.
Zurück zum Zitat Wang X, Wang J, Ma H, Zhang J, Zhou X. Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer. Med Oncol. 2012;29(2):919–27.CrossRefPubMed Wang X, Wang J, Ma H, Zhang J, Zhou X. Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer. Med Oncol. 2012;29(2):919–27.CrossRefPubMed
Metadaten
Titel
MicroRNA 211 expression is upregulated and associated with poor prognosis in colorectal cancer: a case–control study
verfasst von
Ahmet Taner Sümbül
Bülent Göğebakan
Süleyman Bayram
Celal Yücel Batmacı
Serdar Öztuzcu
Publikationsdatum
01.12.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3708-4

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