Clinical significance of Notch pathway-associated microRNA-107 in pancreatic ductal adenocarcinoma
Abstract
Background & aim: MicroRNAs associated with the Notch pathway play a critical role in the progression of pancreatic carcinoma. Our aim was to study the clinical significance of miR-107 and NOTCH2 in pancreatic ductal adenocarcinoma (PDAC). Methods: The circulating miR-107 levels in PDAC and controls were determined by qPCR. NOTCH2 protein (target) expression in tissue of PDAC, periampullary carcinoma, chronic pancreatitis and normal pancreatic tissue was assessed by immunohistochemistry. Results: The circulating miR-107 levels were found to be significantly reduced in PDAC as compared with controls. Additionally, NOTCH2 protein expression was higher in PDAC tissue as compared with controls and was clinically associated with metastasis. Conclusion: Our findings demonstrate the utility of circulating miR-107 as a potential differentiating marker in PDAC.
Papers of special note have been highlighted as: • of interest
References
- 1. CancerNet. Pancreatic cancer: statistics. www.cancer.net/cancer-types/pancreatic-cancer/statistics
- 2. . Pancreatic ductal adenocarcinoma epidemiology and risk assessment: could we prevent? Possibility for an early diagnosis. Endosc. Ultrasound 6(Suppl. 3), S58–S61 (2017).
- 3. . Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74(11), 2913–2921 (2014).
- 4. . Pancreatitis is a risk factor for pancreatic cancer. Gastroenterology 109(1), 247–251 (1995).
- 5. American Cancer Society. Pancreatic cancer risk factors. www.cancer.org/cancer/pancreatic-cancer/causes-risks-prevention/risk-factors.html
- 6. Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig. Dis. Sci. 44(7), 1303–1311 (1999).
- 7. . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2), 281–297 (2004). • Demonstrates the role of epigenetic factor like miRNAs in disease pathogenesis.
- 8. . MicroRNA signatures in human cancers. Nat. Rev. Cancer 6(11), 857–866 (2006). • Focuses on the role of miRNAs in human cancers including pancreatic cancer.
- 9. . The role of Notch signaling and leptin–Notch crosstalk in pancreatic cancer. Medicines (Basel) 5(3), 68 (2018). • Reveals the role of developmental Notch pathway in PDAC.
- 10. . Role of Notch signaling pathway in pancreatic cancer. Am. J. Cancer Res. 7(2), 173–186 (2017). • Unravels the mechanism of Notch signaling pathway activation in pancreatic cancer.
- 11. Targeting the Notch signaling pathway in cancer therapeutics. Thorac. Cancer 5(6), 473–486 (2014).
- 12. . Cross-regulation between Notch signaling pathway and miRNA machinery in cancer. DNA Repair (Amst.) 66–67, 30–41 (2018).
- 13. . Tumors of the ampulla of vater: histopathologic classification and predictors of survival. J. Am. College Surgeons 207(2), 210–218 (2008).
- 14. . Pancreatic carcinoma. N. Engl. J. Med. 326(7), 455–465 (1992).
- 15. . Molecular biology of pancreatic ductal adenocarcinoma progression: aberrant activation of developmental pathways. Prog. Mol. Biol. Transl. Sci. 97, 41–78 (2010).
- 16. . MicroRNA-107 inhibits gastric cancer cell proliferation and metastasis by targeting PI3K/AKT pathway. Microb. Pathog. 121, 110–114 (2018).
- 17. . miR-107 functions as a tumor suppressor in human esophageal squamous cell carcinoma and targets Cdc42. Oncol. Rep. 37(5), 3116–3127 (2017).
- 18. MicroRNA-107-5p suppresses non-small cell lung cancer by directly targeting oncogene epidermal growth factor receptor. Oncotarget 8(34), 57012–57023 (2017).
- 19. . miRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer. Am. J. Cancer Res. 7(9), 1863–1873 (2017).
- 20. . Decreased levels of circulating and tissue miR-107 in human esophageal cancer. Biomarkers 18(4), 322–330 (2013).
- 21. p53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2. Neurosci. Lett. 534, 327–332 (2013).
- 22. . miRNA-107 inhibits proliferation and migration by targeting CDK8 in breast cancer. Int. J. Clin. Exp. Med. 7(1), 32–40 (2014).
- 23. miR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer. BMC Cancer 14, 656 (2014).
- 24. Upregulation of miR-107 inhibits glioma angiogenesis and VEGF expression. Cell. Mol. Neurobiol. 36(1), 113–120 (2016).
- 25. miR-107 regulates tumor progression by targeting NF1 in gastric cancer. Sci. Rep. 6, 36531 (2016).
- 26. Deregulated expression of miR-107 inhibits metastasis of PDAC through inhibition PI3K/Akt signaling via caveolin-1 and PTEN. Exp. Cell Res. 361(2), 316–323 (2017).
- 27. Depleted tumor suppressor miR-107 in plasma relates to tumor progression and is a novel therapeutic target in pancreatic cancer. Sci. Rep. 7(1), 5708 (2017).
- 28. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc. Natl Acad. Sci. USA 107(30), 13438–13443 (2010).
- 29. Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer. Biomed. Rep. 5(3), 344–348 (2016).
- 30. Loss of miR-107, miR-181c and miR-29a-3p promote activation of Notch2 signaling in pediatric high-grade gliomas (pHGGs). Int. J. Mol. Sci. 18(12), 2742 (2017). • Shows dysregulated expression of miR-107 in gliomas.