Abstract
Background
Aberrant expression of microRNAs (miRNAs) has been implicated in the etiopathogenesis and development of various cancers. Drosha and Dicer are the main components of the miRNA biosynthesis machine. Another enzyme, DGCR8, is the assistant of Drosha in the processing complex. Here, we tried to evaluate the mRNA transcript level of Drosha, Dicer, and DGCR8 genes in involved tissues from patients with gastric cancer.
Methods
Fifty tumoral and their marginal tissues, as the control group, were obtained from patients with gastric cancer. After RNA extraction from tissues and cDNA synthesis, quantification of mRNA expression of Drosha, Dicer, and DGCR8 was conducted using SYBR Green master mix and real-time PCR.
Results
It was observed that mRNA expression levels of Drosha, Dicer, and DGCR8 were significantly upregulated in tumoral tissues compared with marginal tissues. Upregulation of these genes was not correlated with clinical manifestations of the patients.
Conclusions
Upregulation of Drosha, Dicer, and DGCR8 plays a role in the development of cancer, probably through dysregulated the expression level of miRNAs.
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References
Alberts S, Cervantes A, Van de Velde C. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003;14(90002):31–6.
Kobayashi T, Kikuchi S, Lin Y, Yagyu K, Obata Y, Ogihara A, et al. Trends in the incidence of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy. Gastric Cancer. 2004;7(4):233–9.
Cowland JB, Hother C, Grønbaek K. MicroRNAs and cancer. Apmis. 2007;115(10):1090–106.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.
Guo J, Miao Y, Xiao B, Huan R, Jiang Z, Meng D, et al. Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol. 2009;24(4):652–7.
Landi D, Gemignani F, Barale R, Landi S. A catalog of polymorphisms falling in microRNA-binding regions of cancer genes. DNA Cell Biol. 2008;27(1):35–43.
Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21(17):4663–70.
Gregory RI, K-p Y, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, et al. The microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432(7014):235–40.
Han J, Lee Y, Yeom K-H, Kim Y-K, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18(24):3016–27.
Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004;14(23):2162–7.
Liao R, Sun J, Zhang L, Lou G, Chen M, Zhou D, et al. MicroRNAs play a role in the development of human hematopoietic stem cells. J Cell Biochem. 2008;104(3):805–17.
Katada T, Ishiguro H, Kuwabara Y, Kimura M, Mitui A, Mori Y, et al. microRNA expression profile in undifferentiated gastric cancer. Int J Oncol. 2009;34(2):537.
Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J, et al. Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 2009;125(11):2737–43.
Tsai KW, Wu CW, Hu LY, Li SC, Liao YL, Lai CH, et al. Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. Int J Cancer. 2011;129(11):2600–10.
Karaayvaz M, Zhai H, Ju J. miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer. Cell Death Dis. 2013;4(6):e659.
Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11(2):136–46.
Asadi M, Shanehbandi D, Mohammadpour H, Hashemzadeh S, Sepehri B. Expression level of miR-34a in tumor tissue from patients with esophageal squamous cell carcinoma. J Gastrointest Cancer. 2018. https://doi.org/10.1007/s12029-018-0060-0.
Sand M, Skrygan M, Georgas D, Arenz C, Gambichler T, Sand D, et al. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinog. 2012;51(11):916–22.
Sand M, Gambichler T, Skrygan M, Sand D, Scola N, Altmeyer P, et al. Expression levels of the microRNA processing enzymes Drosha and dicer in epithelial skin cancer. Cancer Investig. 2010;28(6):649–53.
Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001;29(9):e45.
Rugge M, Fassan M, Graham D. Epidemiology of gastric cancer. In: Strong V, editor. Gastric Cancer. Cham: Springer; 2015.
Somi MH, Farhang S, Mirinezhad SK, Naghashi S, Seif-Farshad M, Golzari M. Cancer in East Azerbaijan, Iran: results of a population-based cancer registry. Asian Pac J Cancer Prev. 2008;9(2):327–30.
DanM F. Survival prediction of gastric cancer by a seven-microRNA signature. Gut. 2009;2008:175497.
Horikawa Y, Wood CG, Yang H, Zhao H, Ye Y, Gu J, et al. Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. Clin Cancer Res. 2008;14(23):7956–62.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.
Rosenfeld N, Aharonov R, Meiri E, Rosenwald S, Spector Y, Zepeniuk M, et al. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008;26(4):462–9.
Volinia S, Calin GA, Liu C-G, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61.
Jafari N, Dogaheh HP, Bohlooli S, Oyong GG, Shirzad Z, Alibeiki F, et al. Expression levels of microRNA machinery components Drosha, Dicer and DGCR8 in human (AGS, HepG2, and KEYSE-30) cancer cell lines. Int J Clin Exp Med. 2013;6(4):269–74.
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9.
Grelier G, Voirin N, Ay A, Cox D, Chabaud S, Treilleux I, et al. Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. Br J Cancer. 2009;101(4):673–83.
Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol RW, et al. Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res. 2007;67(5):2345–50.
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509–24.
Acknowledgements
We are deeply thankful of our patients for their contribution.
Funding
This study was supported by a grant from Tabriz University of Medical Sciences (Grant No. 94-06-21-4112).
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The Human Research Ethics Committees from the Tabriz University of Medical Sciences approved the protocol of this study and written informed consent was taken by all patients.
Conflict of Interest
The authors declare that they have no conflict of interest.
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Asadi, M., Shanehbandi, D., Zafari, V. et al. Transcript Level of MicroRNA Processing Elements in Gastric Cancer. J Gastrointest Canc 50, 855–859 (2019). https://doi.org/10.1007/s12029-018-0154-8
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DOI: https://doi.org/10.1007/s12029-018-0154-8