miRNA-192, miRNA-21 and miRNA-200: new pancreatic cancer markers in diabetic patients?
Authors:
Pavel Škrha 1; Aleš Hořínek 2; Michal Anděl 1; Jan Škrha 2
Authors‘ workplace:
II. interní klinika 3. LF UK a FN Královské Vinohrady Praha, přednosta prof. MUDr. Michal Anděl, CSc.
1; III. interní klinika 1. LF UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA
2
Published in:
Vnitř Lék 2015; 61(4): 351-354
Category:
Original Contributions
Overview
Introduction:
Newly-onset diabetes mellitus (DM) in middle-aged and older people may be an early symptom of pancreatic cancer (PC). However, sensitive markers for PC are still missing. MicroRNAs (miRNAs) play an important role in a cell response regulation. Significant changes in miRNA expressions were observed in cancers. Our goal was to compare expressions of selected miRNAs in patients with PC, DM and controls.
Methods:
We enrolled 74 patients with PC (42/32, with/without DM), 29 type 2 diabetic patients and 17 controls. MicroRNA was determined in serum of all examined subjects. In 9 patients with PC the tumor was resected subsequently and after 3 months the measurements were repeated. We analyzed the expressions of 8 miRNAs that we had identified in a previous pilot study (miR-21, miR-30, miR-191, miR-192, miR-196, miR-200, miR-423, miR-454).
Results:
MicroRNA expressions were significantly higher in patients with PC than in DM and controls: miR-192: 1.6 (1.2 to 2.0) vs 0.3 (0.2–0.4) vs 0.3 (0.2 to 0.5), p < 0.00001; miR-21: 1.4 (1.2–1.7) vs 0.3 (0.2 to 0.5) vs 0.5 (from 0.4 to 0.7), p < 0.00001, miR-200: 1.6 (1.1 to 2.3) vs 0.3 (0.3–0.4) vs 0.3 (0.2 to 0.4), p < 0.00001. No difference was observed between DM and controls, as well as between diabetic and non-diabetic patients within the PC group. There were no significant differences in miRNA expressions in 9 patients after pancreatic surgery. But there were significant interindividual differences.
Conclusion:
Our data shows that miR-21, miR-192 and miR-200 could be used as new diagnostic markers for pancreatic cancer. A dynamics of these miRNAs could serve as a prognostic marker in patients after cancer removal. Futher prospective studies with newly-onset diabetic patients with no signs of malignancy will be needed to validate if suggested miRNAs could be used as early markers as well.
Key words:
diabetes mellitus – microRNA – miRNA-21 – miRNA-192 – miRNA-200 – pancreatic cancer
Sources
1. Epidemiologie zhoubných nádorů v České republice. Dostupné z WWW:
2. Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005; 92(11): 2076–2083.
3. Chari ST, Leibson CL, Rabe KG et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008; 134(1): 95–101.
4. Komatsu S, Ichikawa D, Takeshita H et al. Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma. Br J Cancer 2011; 105(1): 104–111.
5. Tsujiura M, Ichikawa D, Komatsu S et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer 2010; 102(7): 1174–1179.
6. Xu J, Wu C, Che X et al. Circulating MicroRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog 2011; 50(2): 136–142.
7. Wang J, Chen J, Chang P et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila) 2009; 2(9): 807–813.
8. Tang D, Shen Y, Wang M et al. Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer. Eur J Cancer Prev 2013; 22(6): 540–548.
9. Kumar S, Keerthana R, Pazhanimuthu A et al. Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients. Indian J Biochem Biophys 2013; 50(3): 210–214.
10. Feng YH, Wu CL, Tsao CJ et al. Deregulated expression of sprouty2 and microRNA-21 in human colon cancer: Correlation with the clinical stage of the disease. Cancer Biol Ther 2011; 11(1): 111–121.
11. Ramaswamy S, Nakamura N, Vazquez F et al. Regulation of G(1) progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci USA 1999; 96(5): 2110–2115.
12. Kandel ES, Skeen J, Majewski N et al. Activation of Akt/Protein Kinase B Overcomes a G(2)/M Cell Cycle Checkpoint Induced by DNA Damage. Mol Cell Biol 2002; 22(22): 7831–7841.
13. Yang S-m, Huang C, Li X-f et al. miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology 2013; 306: 162–168.
14. Zhao Y, Zhao L, Ischenko I et al. Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer. Target Oncol 2015; epub v tisku.
15. Song B, Wang Y, Kudo K et al. miR-192 Regulates Dihydrofolate Reductase and Cellular Proliferation through the p53-microRNA Circuit. Clin Cancer Res 2008; 14(24): 8080–8086.
16. Zhao C, Zhang J, Zhang S et al. Diagnostic and biological significance of microRNA-192 in pancreatic ductal adenocarcinoma. Oncol Rep 2013; 30(1): 276–84.
17. Feng B, Wang R, Chen LB. Review of MiR-200b and cancer chemosensitivity. Biomed Pharmacother 2012; 66(6): 397–402.
18. Mees ST, Mardin WA, Wendel C et al. EP300 – a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. Int J Cancer 2010; 126(1): 114–124.
19. Huang F, Tang J, Zhuang X et al. MiR-196a Promotes Pancreatic Cancer Progression by Targeting Nuclear Factor Kappa-B-Inhibitor Alpha. PLoS ONE 2014; 9(2): e87897. Dostupné z DOI: <http://doi: 10.1371/journal.pone.0087897>.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2015 Issue 4
Most read in this issue
- Myokines – muscle tissue hormones
- The treatment of diabetes in patients with liver and renal impairment
- Treatment of GLP1 receptor agonists and body mass control
- Treatment of hypertension in diabetes mellitus