Skip to main content
Erschienen in: Journal of Gastrointestinal Cancer 2/2019

06.02.2018 | Original Research

MicroRNA Expression Levels and Histopathological Features of Colorectal Cancer

verfasst von: Sahar Sarmasti Emami, Abolfazl Akbari, Ali-Akbar Zare, Shahram Agah, Mohsen Masoodi, Atefeh Talebi, Sara Minaeian, Azam Fattahi, Farahnaz Moghadamnia

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Non-coding RNAs have opened a new window in cancer biology. MicroRNAs (miRNAs), as a family of non-coding RNAs, play an important role in the gene regulation. The aberrant expression of these small molecules has been documented to involve in colorectal cancer (CRC) pathogenesis. This study aimed to examine the expression of miRNAs in CRC and to correlate their expression levels with histological markers (Ki-67 and CD34).

Materials and Methods

Tumor tissues and matched normal adjacent tissues were collected from 36 patients with newly diagnosed CRC. Immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. A polyadenylation SYBER Green quantitative real-time PCR technique was used to quantify the expression of a panel of five CRC-related miRNAs (hsa-miR-21, 31, 20a, 133b, and 145). Histopathological (H) scores and miRNA expression levels were correlated with clinicopathological features including the degree of differentiation, staging, and lymphovascular invasion.

Results

Our results showed the significant difference between the two groups for the expression level of hsa-miR-21, hsa-miR-31, hsa-miR-145, and miR-20a (P < 0.001), but not for hsa-miR-133b (P = 0.57). Further analysis revealed an inverse significant correlation between hsa-miR-145 and Ki-67 (r = − 0.942, P < 0.001). While a positive correlation was observed between hsa-miR-21 and Ki-67 (r = 0.920, P < 0.001), and hsa-miR-21 and CD34 (r = 0.981, P < 0.001). Also, a positive correlation between hsa-miR-31 and Ki-67 (r = 0.913, P < 0.001), hsa-miR-31 and CD34 (r = 0.798, P < 0.05), hsa-miR-20a and Ki-67 (r = 0.871, P < 0.001), and hsa-miR-20a and CD34 (r = 0.890, P < 0.001) was found.

Conclusion

Dysregulation of miRNAs and correlation with molecular histopathology indicate a biological role for miRNAs in various cellular processes including cell proliferation and angiogenesis in CRC development. On the other hand, the pattern of miRNA expression and its correlation with histological markers are potentially valuable to apply as diagnostic biomarkers for CRC.
Literatur
2.
Zurück zum Zitat Akbari A, Amanpour S, Muhammadnejad S, Ghahremani M, Ghaffari S, Dehpour A, 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(1):47. https://doi.org/10.1186/2008-2231-22-47. Akbari A, Amanpour S, Muhammadnejad S, Ghahremani M, Ghaffari S, Dehpour A, 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(1):47. https://​doi.​org/​10.​1186/​2008-2231-22-47.
3.
Zurück zum Zitat 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. 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.
5.
Zurück zum Zitat Akbari 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: APJCP. 2017;18(8):2101.6. Akbari 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: APJCP. 2017;18(8):2101.6.
6.
Zurück zum Zitat 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. MAZU-CMM. 2017;3(1):25–9.CrossRef 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. MAZU-CMM. 2017;3(1):25–9.CrossRef
9.
Zurück zum Zitat Espinosa CES, Slack FJ. Cancer issue: the role of microRNAs in cancer. Yale J Biol Med. 2006;79(3–4):131. Espinosa CES, Slack FJ. Cancer issue: the role of microRNAs in cancer. Yale J Biol Med. 2006;79(3–4):131.
11.
Zurück zum Zitat 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. 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.
14.
Zurück zum Zitat 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. 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.
15.
Zurück zum Zitat Akbari A, 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(1):1.CrossRef Akbari A, 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(1):1.CrossRef
16.
Zurück zum Zitat Akbari, A., et al. 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). Akbari, A., et al. 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).
17.
Zurück zum Zitat Karimi A, Majidzadeh-A K, Madjd Z, et al. Effect of copper sulfate on expression of endogenous L1 retrotransposons in HepG2 cells (hepatocellular carcinoma). Biol Trace Elem Res. 2015;165:131–4.CrossRefPubMed Karimi A, Majidzadeh-A K, Madjd Z, et al. Effect of copper sulfate on expression of endogenous L1 retrotransposons in HepG2 cells (hepatocellular carcinoma). Biol Trace Elem Res. 2015;165:131–4.CrossRefPubMed
18.
Zurück zum Zitat 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.PubMedPubMedCentral 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.PubMedPubMedCentral
19.
Zurück zum Zitat 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 Biomark. 2016;17(3):301–11. https://doi.org/10.3233/CBM-160642. 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 Biomark. 2016;17(3):301–11. https://​doi.​org/​10.​3233/​CBM-160642.
23.
Zurück zum Zitat Llombart-Bosch, A., et al., Cancer: clinical background and key challenges, in Cancer systems biology, bioinformatics and medicine. 2011, Springer. p. 29–93. Llombart-Bosch, A., et al., Cancer: clinical background and key challenges, in Cancer systems biology, bioinformatics and medicine. 2011, Springer. p. 29–93.
24.
Zurück zum Zitat Molina R, Filella X, Aug&eacute JM, Fuentes R, Bover I, Rifa J, et al. Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Tumor Biol. 2003;24(4):209–18. https://doi.org/10.1159/000074432. Molina R, Filella X, Aug&eacute JM, Fuentes R, Bover I, Rifa J, et al. Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Tumor Biol. 2003;24(4):209–18. https://​doi.​org/​10.​1159/​000074432.
27.
Zurück zum Zitat zur Hausen H. The role of microRNAs in human cancer. Int J Cancer. 2008;122(5):ix–x. zur Hausen H. The role of microRNAs in human cancer. Int J Cancer. 2008;122(5):ix–x.
36.
Zurück zum Zitat Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72(5–6):397–402. https://doi.org/10.1159/000113489. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72(5–6):397–402. https://​doi.​org/​10.​1159/​000113489.
37.
Zurück zum Zitat Qi L, Bart J, Tan LP, Platteel I, Sluis T, Huitema S, et al. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer. 2009;9(1):163. https://doi.org/10.1186/1471-2407-9-163. Qi L, Bart J, Tan LP, Platteel I, Sluis T, Huitema S, et al. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer. 2009;9(1):163. https://​doi.​org/​10.​1186/​1471-2407-9-163.
40.
Zurück zum Zitat Breier G, Albrecht U, Sterrer S, Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 1992;114(2):521–32.PubMed Breier G, Albrecht U, Sterrer S, Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 1992;114(2):521–32.PubMed
51.
53.
Zurück zum Zitat Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Note: Susan M. O'Connor and Nicholas G. van Holst Pellekaan contributed equally to this work. Mol Cancer Res. 2003;1(12):882–91.PubMed Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Note: Susan M. O'Connor and Nicholas G. van Holst Pellekaan contributed equally to this work. Mol Cancer Res. 2003;1(12):882–91.PubMed
55.
Zurück zum Zitat Liu L-Z, Hu XW, Xia C, He J, Zhou Q, Shi X, et al. Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1α expression through activation of AKT and P70S6K1 in human ovarian cancer cells. Free Radic Biol Med. 2006;41(10):1521–33. https://doi.org/10.1016/j.freeradbiomed.2006.08.003. Liu L-Z, Hu XW, Xia C, He J, Zhou Q, Shi X, et al. Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1α expression through activation of AKT and P70S6K1 in human ovarian cancer cells. Free Radic Biol Med. 2006;41(10):1521–33. https://​doi.​org/​10.​1016/​j.​freeradbiomed.​2006.​08.​003.
57.
Zurück zum Zitat Yu Z, Tozeren A, Pestell RG. Function of miRNAs in tumor cell proliferation, in microRNA in cancer. 2013, Springer. p. 13–27. Yu Z, Tozeren A, Pestell RG. Function of miRNAs in tumor cell proliferation, in microRNA in cancer. 2013, Springer. p. 13–27.
58.
Zurück zum Zitat Zhou Q, Liu LZ, Fu B, Hu X, Shi X, Fang J, et al. Reactive oxygen species regulate insulin-induced VEGF and HIF-1α expression through the activation of p70S6K1 in human prostate cancer cells. Carcinogenesis. 2006;28(1):28–37. https://doi.org/10.1093/carcin/bgl085. Zhou Q, Liu LZ, Fu B, Hu X, Shi X, Fang J, et al. Reactive oxygen species regulate insulin-induced VEGF and HIF-1α expression through the activation of p70S6K1 in human prostate cancer cells. Carcinogenesis. 2006;28(1):28–37. https://​doi.​org/​10.​1093/​carcin/​bgl085.
Metadaten
Titel
MicroRNA Expression Levels and Histopathological Features of Colorectal Cancer
verfasst von
Sahar Sarmasti Emami
Abolfazl Akbari
Ali-Akbar Zare
Shahram Agah
Mohsen Masoodi
Atefeh Talebi
Sara Minaeian
Azam Fattahi
Farahnaz Moghadamnia
Publikationsdatum
06.02.2018
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 2/2019
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-018-0055-x

Weitere Artikel der Ausgabe 2/2019

Journal of Gastrointestinal Cancer 2/2019 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.